Tesis sobre el tema "Dynamiques en cellules uniques"
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Deprez, Marie. "Étude de l’hétérogénéité cellulaire et des dynamiques de régénération de l’épithélium respiratoire sain par analyses des signatures transcriptionnelles sur cellules uniques". Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR6022.
Texto completoImprovements made in nucleic acid sequencing and cell handling technologies now offer the opportunity to analyze simultaneously the content of numerous single cells (RNA, DNA, ...) by global and unbiased approaches. This single-cell ‘omics’ revolution provides a new framework to revisit the “Cell Theory”, elaborated over several centuries, and essentially based on morphological and functional features. The many cell modalities now accessible at single- cell level, such as their transcriptome, spatial localization, developmental trajectories, enrich considerably this definition, and set a renewed context to precisely reassess the definition of ‘cell types’, ‘cell states’ as well as their different interactions and fates.My thesis work initially set up ad hoc approaches and statistical framework to analyze appropriately these single-cell data, which deeply differ from standard bulk RNA-seq. High variance, presence of a huge percentage of null values, large volume of data are among the specific characteristics of these datasets. My work was centered on the main experimental model of my host laboratory, e.g. the human airway epithelium. Human airways are lined by a pseudostratified epithelium mainly composed of basal, secretory, goblet and multiciliated cells. Airways also constitute a true cellular ecosystem, in which the epithelial layer interacts closely with immune and mesenchymal cells. This coordination between cells ensures proper defense of the respiratory system and its correct regeneration in case of external aggression and injuries. A better understanding of the operating sequences in normal and physiopathological situations is relevant in pathologies such as chronic obstructive pulmonary disease, asthma or cystic fibrosis.First, I characterized at a single cell level the precise and cell-specific sequence of events leading to functional regeneration of the epithelium, using a 3D model of human cells. I then built a single-cell atlas of the different cell types that are lining healthy human airways from the nose to the 12th generation of bronchi.By applying computational and statistical approaches, I have identified cell lineage hierarchies and was able to reconstruct a comprehensive cell trajectory roadmap in human airways. I not only confirmed previously described cell lineages, but I have also discovered a novel trajectory that links goblet cells to multiciliated cells, identifying novel cell populations and molecular interactors involved in the process of healthy human airway epithelium regeneration. The profiling of 12 healthy volunteers then generated a dataset of 77,969 cells, derived from 35 distinct locations. The resulting atlas is composed of more than 26 epithelial, immune and stromal cell types demonstrating the cellular heterogeneity present in the airways. Its analysis has revealed a strong proximo-distal gradient of expression in suprabasal, secretory, or multiciliated cells between the nose and lung airways. My work has also improved the characterization of rare cells, including “hillock” cells that have been previously described in mice.In conclusion, this work probably represents one of the first single-cell investigations in human airways. It brings original contributions to our understanding of differentiation’s dynamics and cellular heterogeneity in healthy human airways. The resulting resource will be extremely useful for any future single-cell investigators and also for establishing a very useful joint between clinical and biological works. As such, it will constitute a reference in any future project aiming to precisely analyze specific disease conditions
Bachy, Charles. "Phylogénie, diversité et dynamique temporelle chez les ciliés tintinnidés marins". Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00769949.
Texto completoChalabi, Asma. "Processus d'analyse dynamique pour l'imagerie de cellules vivantes permettant la détection des réponses cellulaires aux anticancéreux, par traitement de l'image et du signal et apprentissage automatique profond". Electronic Thesis or Diss., Université Côte d'Azur, 2024. http://www.theses.fr/2024COAZ6004.
Texto completoCell division and cell death are the main indicators to evaluate cancer drug action, and only their accurate measures can reveal the actual potency and efficacy of a compound. The detection of cell division and cell death events in live-cell assays has the potential to produce robust metrics of drug pharmacodynamics and return a more comprehensive understanding of tumor cells responses to cancer therapeutic combinations. Knowing precisely when a cell death or a cell division occurs in a live-cell experiment allows to study the relative contribution of different drug effects -such as cytotoxic or cytostatic effects, on a cell population. Yet, classical methods require dyes to measure cell viability as an end-point assay with whole population counts, where the proliferation rates can only be estimated when both viable and dead cells are labeled simultaneously.Live-cell imaging is a promising cell-based assay to determine drug efficacies, with the main limitation being the accuracy and depth of the analyses to detect and predict automatically cellular response phenotypes (cell death and division, which share some morphological features).This thesis introduces a method integrating deep learning using neural networks, and image and signal processing to perform dynamic image analyses of single-cell events in time-lapse microscopy experiments of drug pharmacological profiling. This method works by automatically tracking the cells, extracting radiometric and morphologic cell features, and analyzing the temporal evolution of these features for each cell so as to detect cellular events such as division and cell death, as well as acquiring signaling pathway dynamics.A case of study comprising the analyses of caspase-8 single-cell dynamics and other cell responses to cancer drugs is presented. The aim is to achieve automatically, at a large scale the necessary analyses to augment the phenotype prediction method available in the lab (Fateseq) and to apply it to various cancer cell lines of a human cancer cell line panel to improve our live-cell OMICS profiling approaches, and, in a longer term, to scale up pharmacological screening of new cancer drugs
Moussy, Alice. "Caractérisation des premières étapes de différenciation des cellules hématopoïétiques à l'échelle de la cellule unique". Thesis, Paris Sciences et Lettres (ComUE), 2017. http://www.theses.fr/2017PSLEP029/document.
Texto completoDespite intensively studies, the fundamental mechanisms of cell fate decision during cellular differentiation still remain unclear. The deterministic mechanisms, often based on studies of large cell populations, cannot explain the difference between individual cell fates choices placed in the same environment. The aim of my thesis work is to study the first steps of hematopoietic cell differentiation at the single cell level thanks to transcriptomic, proteomic and morphological analyses. Two differentiation models have been used: T regulatory lymphocytes and human cord blood-derived CD34+ cells. The behavior of individual cells following stimulation has been analyzed. Using time-lapse microscopy coupled to single cell molecular analyses, we could demonstrate that the cell fate choice is not a unique, programmed event. First, the cell reaches a metastable “multi-primed” state, which is characterized by a mixed lineage gene expression pattern. After transition through an “uncertain”, unstable state, characterized by fluctuations between two phenotypes, the cell reaches a stable state. Our observations are coherent with a stochastic model of cell fate decision. The differentiation is likely to be a spontaneous, dynamic, fluctuating and not a deterministic process. The cell fate decisions are taken by individual cells
Labrunie, Antoine. "Matériaux « uniques » pour cellules solaires organiques mono-composant". Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0044/document.
Texto completoOver the last few years, the development of bulk heterojunction organic solar cells (BHJ OSCs) led to significant increase in photovoltaic (PV) efficiency. Such devices are based on interpenetrated networks of an electron-donor material (D) and an electron-acceptor material (A) constituting the active layer. Nevertheless a careful optimization of the morphology is required to reach high power conversion efficiency. Furthermore, this optimized morphology can evolve towards spontaneous phase segregation which can be detrimental for the PV performances. To circumvent these limitations, a relatively unexplored approach relies on the use of a material where the donor and the acceptor moieties are covalently linked to each other through a nonconjugated π-connector. In this context, the work reported herein describes the synthesis and characterization of various molecular D-σ-A assemblies, as well as their preliminary evaluation as “unique” material for the realisation of single component organic solar cells (SC-OSCs). A first family of dyads and triads, based on quaterthiophene moieties as donor block, was studied. A general methodology to assemble the two D and A blocks via a Huisgen-type click-chemistry is described. Then, in the next chapters, several dyads based on a “push-pull” donor block have been synthesized and characterized. The PV performances of these compounds have been evaluated in SC-OSCs leading to power conversion efficiency up to 1.4 %, a value close to the state of the art
Geisler, Hubert. "Structuration d'hydrogels thermoactivables pour l'analyse de cellules uniques". Electronic Thesis or Diss., Université Paris sciences et lettres, 2020. http://www.theses.fr/2020UPSLS001.
Texto completoWe present in this work a new microfluidic technology aiming at isolating single cells by the use of thermoactuable polymers. One of the polymers we use is polyNIPAM, a polymer that can expand its volume by 400% in water when the temperature is set under 32°C and can shrink down when it is set over 34°C. We use this reversible swelling capability to open and close compartments embedded in a microfluidic chip.Grafting and structuring these hydrogel features relies on thiol-en click chemistry, initiated thermally or by UV irradiation. We have developed methods and microfabrication protocols in order to diversify the substrate materials (from glass to PDMS, COC, PMMA, etc), to expand the structures thickness range (from few microns to a tenth of microns) and to strengthen our knowledge regarding the fabrication impact on the hydrogel’s behavior. A robust protocol of photolithography has finally been worked on allowing the design of any type of 2D features on a large choice of substrates.One of the realistic applications detailed here is the development of microfluidic chips aiming at isolating single cells in hydrogel compartments. (confidential)
Vianay, Benoit. "Adhérence de cellules uniques sur supports micro-structurés". Phd thesis, Grenoble 1, 2009. http://www.theses.fr/2009GRE10329.
Texto completoThe cell adhesion is a critical process involved in many fundamental biological phenomena as dierentiation, tissue repair or cell development. This thesis focuses on a study combining experiments and modelization of single cells spreading on micro-fabricated substrates. Experimental results show that the geometrical constraint imposed by the adhesiveness contrast limits the adhesion. Beyond this limitation, a reproducible organization of the actin cytoskeleton of cells spreading on micro-structured materials suggests that simple physical laws govern the process. We have developed a classication method of basic geometrical shapes observed experimentally to obtain robust statistics. Based on the Cellular Potts model, we reproduced experimental results. This energetical model shows that the basic shapes are metastable states used by cells during spreading. The model parameters are linked to relevant biological parameters. We present results that connect the curvature of interfaces to biological parameters. We show that the experimental measurement of this curvature represents the competition between the contractility of stress bers and the elasticity of the actin gel. A correspondence between the physical properties in the model and the biochemical processes that regulate and organize the cellular adhesion is possible
Vianay, Benoit. "Adhérence de cellules uniques sur supports micro-structurés". Phd thesis, Grenoble 1, 2009. http://tel.archives-ouvertes.fr/tel-00455350.
Texto completoCaccianini, Laura. "Imagerie de l'architecture dynamique de la chromatine dans la cellule unique". Thesis, Paris Sciences et Lettres (ComUE), 2019. https://tel.archives-ouvertes.fr/tel-02896692.
Texto completoChromatin structure and cellular function are tightly linked in the nucleus of mammalian cells. Disruption of chromatin spatial organisation dramatically affects the life of a cell and eventually leads to severe pathologies in entire organisms. Two nuclear factors, CTCF and Cohesin, have been found to play a crucial role in the regulation and maintenance of DNA architecture. Huge advancements have been made in the understanding of the mechanisms behind chromatin arrangement but the field is still lacking a dynamic picture at the single cell and single molecule level. This study provide this study provides insight into the dynamics of CTCF and Cohesin through single particle tracking of CTCF and Cohesin dynamics achieved with single molecule tracking in living mouse embryonic stem cells. The interplay between these two factors was studied by looking at Cohesin’s behaviour in the absence of CTCF and in the context of other biological alterations
Chaste, Julien. "Transistors à nanotube de carbone unique : propriétés dynamiques et électrons uniques". Paris 6, 2009. https://tel.archives-ouvertes.fr/tel-00420915.
Texto completoChaste, Julien. "Transistors à nanotube de carbone unique : propriétés dynamiques et détection d'électrons uniques". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2009. http://tel.archives-ouvertes.fr/tel-00420915.
Texto completoLa quantification des électrons dans le nanotube joue un rôle sur la limitation de la conductance, de la transconductance gm, de la capacité de grille Cg et en particulier sur la limitation de la fréquence de coupure ωt=gm/Cg par l'inductance cinétique du canal.
Les deux montages expérimentaux, l'un à 300K et l'autre à 4K, ainsi que la fabrication des NT-FET ont intégré des solutions efficaces au problème de désadaptation d'impédance et ont permis de mesurer la transmission entre 0,1 et 1,6GHz ainsi que gm,Cg et ωt. Des fréquences ωt =50GHz ont même été mesurées.
De plus, la coloration du bruit (0,2-0,8GHz) du transistor à 4K a été déterminée. Le bruit mesuré en mode ouvert est d'origine poissonienne (F=1) et montre des effets de saturation dues aux phonons optiques.
L'ensemble de ce travail a prouvé que la résolution de charge δqrms du NT-FET est suffisante pour détecter des charges uniques en une nanoseconde
Bonnaffoux, Arnaud. "Inférence de réseaux de régulation de gènes à partir de données dynamiques multi-échelles". Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEN054/document.
Texto completoInference of gene regulatory networks from gene expression data has been a long-standing and notoriously difficult task in systems biology. Recently, single-cell transcriptomic data have been massively used for gene regulatory network inference, with both successes and limitations.In the present work we propose an iterative algorithm called WASABI, dedicated to inferring a causal dynamical network from timestamped single-cell data, which tackles some of the limitations associated with current approaches. We first introduce the concept of waves, which posits that the information provided by an external stimulus will affect genes one-byone through a cascade, like waves spreading through a network. This concept allows us to infer the network one gene at a time, after genes have been ordered regarding their time of regulation. We then demonstrate the ability of WASABI to correctly infer small networks, which have been simulated in-silico using a mechanistic model consisting of coupled piecewise-deterministic Markov processes for the proper description of gene expression at the single-cell level. We finally apply WASABI on in-vitro generated data on an avian model of erythroid differentiation. The structure of the resulting gene regulatory network sheds a fascinating new light on the molecular mechanisms controlling this process. In particular, we find no evidence for hub genes and a much more distributed network structure than expected. Interestingly, we find that a majority of genes are under the direct control of the differentiation-inducing stimulus. Together, these results demonstrate WASABI versatility and ability to tackle some general gene regulatory networks inference issues. It is our hope that WASABI will prove useful in helping biologists to fully exploit the power of time-stamped single-cell data
Pierrat, Sébastien. "Etude de l'adhésion cellulaire à différentes échelles de la molécule unique à la cellule". Paris 6, 2004. http://www.theses.fr/2004PA066485.
Texto completoFoulon, Sophie. "Développement du séquençage ARN ciblé sur cellules uniques en microfluidique de gouttes et applications". Thesis, Paris Sciences et Lettres (ComUE), 2019. http://www.theses.fr/2019PSLET037.
Texto completoSingle cells technologies were introduced a few years ago and have been dramatically evolving ever since. These technologies have revolutionized biology, making it possible to better understand how heterogeneous cell systems works. For example, they permit to discover and follow cell subtypes, with applications in oncology or neurobiology. We have developed a technology to study the expression profile of genes of interest at the level of a single cell, using droplet-based microfluidics. By limiting the number of genes studied compared to commercial whole-transcriptome technologies, the targeted approach has several potential benefits: gaining deeper sequencing, increasing the number of cells studied, optimizing detection for low levels of expression, while reducing the complexity of data and costs. Targeting is sometimes essential, especially when the RNAs do not carry a generic primer sequence, as in the case of viral RNAs. Two applications are presented: the analysis of inflammation of the immune cells of the brain in the early stages of development, as well as the study of genetic recombination in the virus
Lombard, Alain. "QuanTI-FRET, un outil d'imagerie pour l'analyse de la mécanotransduction dans les cellules vivantes uniques". Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALY055.
Texto completoMany elementary cellular processes (migration, differentiation, death) are controled by a set of agents linked together by cascade reactions. Some of these signaling networks convert mechanical signals external to the cell into internal biochemical signals, a process called mechanotransduction. We seek to study these networks through a signal processing approach, in order to experimentally determine an analogous of the transfer function in time and space for mechanotransduction.Controlling the input variable is done by different type of 2D substrates which have been developped, from the simple glass surface, the adherent geometrical patterns, to the magneto-active substrates (composed of micro-pillars inserted into an elastomer) capable of stimulating locally and dynamically the cells.Measuring the biochemical output variable is done by FRET biosensors. The fluorescence emitted is collected through an inverted widefield fluorescence microscope. We set up the quantitative FRET efficiency calculus from this fluorescence without using FRET standards. It gives access to the activity in space and time of some molecules of network signalisation.Some tools are finally presented as potential candidates to perform the transfer function, among them are combination of correlation methods, and singular value decomposition used in acousto-optics. Combiantion of these tools and methods remains complex, particularly to highlight a biological behaviour from a quantitative quantity. The first use of these tools do not give any biological result, but are promising to study mechanotransduction
Traboulsi, Abdel-Meneem. "Étude à moyen-débit de la localisation d'ARNm dans les cellules humaines". Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT117.
Texto completoMRNA localization was discovered in 1983 in ascidian oocytes and early embryos. Since then many examples of localized RNAs have been found in many organisms, including plants, yeast, fungi, insects, fish and mammals. Localized mRNAs contribute to many biological functions, such as embryonic patterning, asymmetric cell division, cell migration, signaling, neuronal plasticity and others…Until now, only few studies analyzed RNA localization in a systematic manner. Three of them were done in Drosophila, during embryogenesis, oogenesis or larval stage and analyzed around 16000 mRNAs in total. The two other studies were done in mammalian cells and analyzed nearly 1000 mRNAs each. These studies opened a door and raised questions regarding the importance of mRNA localization in human cells and its implication in different biological processes. The goal of my thesis was thus to increase the throughput of single molecule FISH techniques (smFISH) and to study mRNA localization in HeLa cells in a systematic manner.One limitation in smFISH is the cost of the fluorescent oligonucleotide probes, which limits the number of mRNAs that can be analyzed. Therefore, I developed an alternative protocol in which probes for many genes were synthesized as a pool of oligonucleotides (40 per gene in average, more than 12000 in total). Gene-specific probes were then amplified by PCR and converted into single strand by in vitro transcription. I generated a complete protocol, starting from probe design and up to image acquisition. I was interested in studying cell cycle genes. Indeed, cell cycle genes have been extensively studied at the protein level but little is known concerning the localization of their mRNAs. During mitosis, cells go through important morphological modifications and local translation could be a mean of achieving protein localization. This screen is ongoing.In parallel to these experiments, I performed a smFISH based screen on 100 randomly chosen genes and 50 regulators of the G2/M transition of the cell cycle, using a traditional smFISH protocol. In this set-up, I took advantage of a library of HeLa cell lines, in which each cell line contains a bacterial artificial chromosome with the gene of interest tagged with GFP. Therefore, using oligonucleotides hybridizing to the GFP sequence, I could use the same probe set to study the localization of all the tagged mRNAs. A further advantage is that protein localization could be assessed simultaneously. My results indicate that two mRNAs showed a specific localization when screening 100 random genes, and 16 mRNAs among the 50 regulators of the G2/M transition. These mRNAs belong to five localization classes: "blobs", which are cytoplasmic mRNA aggregates; "clusters", which are areas of high local mRNA concentration but where individual mRNA can still be resolved; "nuclear envelope", where mRNAs concentrate around the nuclear envelope; "spindle", which are mRNAs accumulating on the cell division apparatus during mitosis, “spots" which are cytoplasmic mRNA aggregates where individual mRNA can’t be resolved and are bigger than blobs. Interestingly, colocalization between mRNA and GFP, which suggests local translation, was only found for 1 mRNA.These random and targeted screens performed at small-scale show an unexpected frequency and diversity in mRNA localization patterns, therefore pointing to new functions related to this process. This will stimulate future studies aiming at performing screenings at a higher scale
Ruiz, Garcia Sandra. "Appréhender l'hétérogénéité cellulaire et la dynamique de différenciation des épithéliums des voies aériennes au moyen de signatures transcriptionnelles sur cellule unique". Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4204/document.
Texto completoHuman airways are lined by a pseudostratified epithelium mainly composed of basal and columnar cells, among these cells we can find multiciliated, secretory cells and goblet cells. All these cells work together in the mucociliary clearance of the airways. This epithelium regenerates slowly under homeostatic conditions but is able to recover quickly after aggressions through proliferation, migration, polarization and differentiation processes. However, in patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease, asthma or cystic fibrosis, epithelial repair is defective, tissue remodeling occurs, leading to loss of multiciliated cells and goblet cell hyperplasia, impairing correct mucociliary clearance. The sequence of cellular events leading to a functional or remodelled tissue are still poorly described. Hence, we aim at identifying the successive cell types appearing during tissue regeneration and the molecular events that are responsible for healthy or pathological regeneration. We have analysed airway epithelial cell composition at several stages of differentiation using an in vitro 3D culture model which reproduces in vivo epithelial cell composition. Applying single cell transcriptomics and computational methods, we have identified cell lineage hierarchies and thus constructed a comprehensive cell trajectory roadmap in human airways. We have confirmed the cell lineages that have been previously described and have discovered a novel trajectory linking goblet cells to multiciliated cells. We have also discovered novel cell populations and molecular interactors involved in the process of healthy human airway epithelium regeneration. Using these approaches, we have finally shed light on cell-type specific responses involved in pathological goblet cell hyperplasia. Our data, by bringing significant contributions to the understanding of differentiation’s dynamics in the context of healthy and pathological human airway epithelium, may lead to the identification of novel therapeutic targets
Lévesque, Lucie. "Étude des effets de contraintes dynamiques sur l'organisation d'échafaudage collagène-cellules". Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27637.
Texto completoIn the last thirty years, vascular tissue engineering has emerged as an important field in tissue engineering due to a significant clinical need for adequate vascular graft for replacement of small diameter artery. Indeed, the current autologous or synthetic grafts of small diameter present a high failure rate within 5 to 10 years. Despite the efforts injected in the recent years, the clinical translation of engineered artery constructs is far from being successful. One of the challenges encountered in tissue engineering is the control of cellular functions that dictates the maturation of tissue engineering constructs. Furthermore, numerous studies have been conducted on the response of smooth muscle cells (SMC) in 2D under cyclic strain, but a few have examined the effect of cyclic strain on SMCs in 3D to optimize the control strategies of bioreactors for tissue maturation and generation. Thus, this research project aims to study the effects of cyclic mechanical stimuli on cellularised collagen scaffolds. Collagen has been used as a scaffold due to its excellent biological properties and since it is found in the wall of physiological arteries. A system for imposing cyclic mechanical stimuli in 2D to 3D cellularised collagen constructs was therefore developed. The cyclic stresses revealed a preferential orientation of the cells in the direction of the strain, as well as an orientation by the cells of the collagen fibrils in the same direction. Moreover, the remodeling performed by the cells led to an improvement of the viscoelastic properties of the construct and to a mechanical behavior similar to the saphenous vein under stress-relaxation. The cells also shown a desensitization to cyclic mechanical stimuli. Thus, this research allowed to answer some of the questions related to cellular behavior in a 3D environment under mechanical stimulation. Deepening our knowledge of cell behavior in 3D environment under cyclic mechanical stimuli remains a key challenge in obtaining regenerated artery with similar physiological properties than native arteries.
Ruiz, Garcia Sandra. "Appréhender l'hétérogénéité cellulaire et la dynamique de différenciation des épithéliums des voies aériennes au moyen de signatures transcriptionnelles sur cellule unique". Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4204.
Texto completoHuman airways are lined by a pseudostratified epithelium mainly composed of basal and columnar cells, among these cells we can find multiciliated, secretory cells and goblet cells. All these cells work together in the mucociliary clearance of the airways. This epithelium regenerates slowly under homeostatic conditions but is able to recover quickly after aggressions through proliferation, migration, polarization and differentiation processes. However, in patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease, asthma or cystic fibrosis, epithelial repair is defective, tissue remodeling occurs, leading to loss of multiciliated cells and goblet cell hyperplasia, impairing correct mucociliary clearance. The sequence of cellular events leading to a functional or remodelled tissue are still poorly described. Hence, we aim at identifying the successive cell types appearing during tissue regeneration and the molecular events that are responsible for healthy or pathological regeneration. We have analysed airway epithelial cell composition at several stages of differentiation using an in vitro 3D culture model which reproduces in vivo epithelial cell composition. Applying single cell transcriptomics and computational methods, we have identified cell lineage hierarchies and thus constructed a comprehensive cell trajectory roadmap in human airways. We have confirmed the cell lineages that have been previously described and have discovered a novel trajectory linking goblet cells to multiciliated cells. We have also discovered novel cell populations and molecular interactors involved in the process of healthy human airway epithelium regeneration. Using these approaches, we have finally shed light on cell-type specific responses involved in pathological goblet cell hyperplasia. Our data, by bringing significant contributions to the understanding of differentiation’s dynamics in the context of healthy and pathological human airway epithelium, may lead to the identification of novel therapeutic targets
Daumas, Frédéric. "Diffusion latérale du récepteur ư aux opioi͏̈des analysée par suivi de particule unique à la surface de cellules vivantes : relation organisation dynamique-fonction". Toulouse 3, 2002. http://www.theses.fr/2002TOU30180.
Texto completoG protein coupled receptors are involved with other partners in a signal transduction pathway whose mechanism is still not completely understood. We used single particle tracking to study the real time lateral movements of the æ opioid receptor on the surface of fibroblast cells stably transfected by a T7-tagged æ opioid receptor. Two populations could be distinguished : 10% of the receptors exhibit a directed diffusion mode and 90% have a "walking confined diffusion" mode combining a short term confined diffusion with a long term random walk. .
Hostein, Richard. "Etudes des propriétés optiques et dynamiques des boîtes quantiques InAsP/InP [001] : application à la réalisation de sources de photons uniques et lasers à cristaux photoniques émettant à 1.5 μm". Paris 6, 2009. https://tel.archives-ouvertes.fr/tel-00439577v2.
Texto completoEisele, Almut. "La cinétique de différentiation des cellules souches hématopoïétiques uniques après transplantation : l´état d´équilibre et l´effet de la cytokine érythropoïétine". Thesis, Paris Sciences et Lettres (ComUE), 2019. https://tel.archives-ouvertes.fr/tel-03028817.
Texto completoHematopoietic cells are the most numerous cells in our body, and their overall short half-life requires their steady production. At the apex of the hematopoietic system resides a small number of hematopoietic stem cells (HSC) which give rise to all mature hematopoietic cell types through self-renewal and differentiation divisions. For long it was assumed that these HSC are a homogeneous population of multipotent cells. Technical advancements, which allowed to trace HSC at the single cell level, revealed however that single HSC behave differently with respect to the number of lineages and the relative amounts of different lineages they produce and are heterogeneous with respect to their long-term engraftment capacity. Notably different lineage restricted and biased cells, as well as cells with long-term and short-term engraftment potential have been identified in the HSC gate. One technique allowing the lineage tracing of single HSC is cellular barcoding, which relies on the introduction of an artificially created DNA fragment, the barcode, in the genome of HSCs through viral transfection. As these barcodes are transmitted to all daughter cells, the analysis of the barcode identity of progeny cells reveals which lineages and how much of each is produced by each individual HSCs.In this thesis we used a new cellular barcoding library to analyze how the different HSC subsets previously described interact and behave in the first six weeks after bulk transplantation, as well as the influence of erythropoietin (EPO) on this process. More in detail, we described the reconstitution kinetics of HSC in the myeloid (M; macrophage, monocytes, neutrophils, eosinophils), lymphoid (B-cells), dendritic cells, megakaryocyte and erythroid lineage (E; erythroblasts) at the single cell level. For the analysis of HSC differentiation towards the erythroid lineage we established the detection of cellular barcodes from RNA. We discovered that HSC clonal succession and clonal stability co-occur in the first weeks after transplantation, but are not evenly distributed over the different hematopoietic lineages. Notably the production of erythroid cells 2-weeks after transplantation was maintained by distinct short-lived HSC clones, while high myeloid cell production after transplantation was guaranteed by long-lived multi-outcome HSCs. In vitro EPO exposure of HSC before transplantation, did not change the overall lineage output of transplanted HSC, or HSC differentiation kinetics, lineage restrictions, and biases at the single cell level in the first six weeks after transplantation. However, after transplantation of EPO-exposed HSC long-lived unbiased multi-outcome HSCs lost preponderance with respect to cellular output. Rather, changing clones of two types of highly biased HSCs, myeloid-erythroid (ME)-biased and myeloid B-cell (MB)-biased HSC, produced now the majority (>60%) of erythroid, myeloid and B-cells. This effect was transient but stable over different EPO concentrations and after in vivo EPO treatment during transplantation. It suggests a functional compensation mechanism at work.We hope the detailed description of the engraftment kinetics of single control and EPO-exposed HSC after bulk transplantation will have relevance both for fundamental research and the clinics
Beuneu, Hélène. "Dynamiques cellulaires des lymphocytes T CD8 et des cellules Natural Killer lors de leur activation par les cellules dendritiques dans le ganglion lymphatique". Paris 11, 2009. http://www.theses.fr/2009PA11T064.
Texto completoCD8 T lymphocytes and Natural Killer (NK) cells are both capable of elimination of infected or turner cells. As is true for T cells, a first interaction between NK cells and dendritic cells (DC) modifies their ability to eliminate target cells. This phenomenon as been reported as « priming » and occurs in the lymph node. It is crucial to understand how and when CD8 T cells and NK cells receive signals from DC and how this process can be regulated. CD4 T cells increase CD8 T cell secondary responses, but their effect on pnmary responses is still controversial. We have developed an experimental model to study the phenomenon of CD4 help. We show that CD4 help increases CD8 T cell capacity to express interleukin-2 receptor and to produce interferon-y during the early phases of the primary response. As early as day one we observe formation of stable clusters containing three cell types: CD8 T cells, CD4 T cells, and DC. Importantly, we show that CD4 help increases DC capacity to interact with CD8 T cells, a phenomenon that is dependent on CD40 engagement on DC surface. We propose that by promoting CD8 T cell-DC encounters, CD4 T cells increase CD8 T cell access to a stimulatory environment. DC are also implicated in NK cell activation following microbial recognition by Toll Like Receptors (TLR). This activation is dependent on NK cell-DC contact, cytokine production IL-15 transpresentation by DC. Using mice in which NK cells and DC express different fluorescent proteins (CDllcYFP x NCRl +/GFP) we have followed endogenous NK cell dynamis at steady state and during activation. We have observed that NK cells are motile, displaying a mean velocity of 9µm/min and establishing numerous transient interactions with DC. NK-DC stable synapses were not detected during activation. Rather, NK cells were found to continuously interact transiently with DC. However, NK cells spend 50% of their time contacting DC so they have ample opportunity to collect information. We propose that by maintaining a high velocity in the lymph node, NK cells efficiently scan a high number of DC and rapidly integrate the local concentration of cytokine produced and presented by the DC network. Finally, observing calcium flux following interaction with DC we suggest that differences in the calcium responses of NK cells and T cells in contact with stimulatory DC provide a plausible explanation for their distinct modes of interaction. To conclude, we can speculate that differences in contact stability correspond to specifie strategies to efficiently collect activating signais that reflect differentiai cellular orchestration between the adaptive and innate immune systems
Mennesson, Eric. "Transport transendothélial de gènes : études dynamiques du passage sélectif de polyplexes à travers l'endothélium vasculaire pulmonaire". Orléans, 2005. http://www.theses.fr/2005ORLE2073.
Texto completoChen, Wenli. "Spectroscopie diélectrique hyperfréquence de cellules uniques cancéreuses : de l'optimisation du capteur en sensibilité et répétabilité jusqu'au suivi en temps réel de stimuli chimiques". Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30219/document.
Texto completoThe measurement of biological cells is a routine step in many biological investigations. Current techniques used by biologists are mainly based on staining or fluorescent labelings, which provide very precise and effective molecular and cellular observations. Within this context, the microwave dielectric spectroscopy for cell analysis represents a new and attractive method, due to the lack of cells preparation and manipulation, without adding chemicals that could interfere with other cellular constituents. Its compatibility with the analysis of single-cells, potentially in real-time monitoring, constitute also two major assets of the analysis technique. This PhD thesis therefore focused on the optimization of a microfluidic and microwave based biosensor, which is dedicated to the dielectric spectroscopy of individual biological cells, and the development of its metrology to assess the dielectric behavior of cells subjected to chemical stimuli. After a state of the art on the current techniques available to analyze single cells, we focused on the optimization of the microwave biosensor to improve its performances in terms of sensitivity and repeatability. These optimizations dealt with the microfabrication process, the component architecture through the investigation of single cell loading efficacy as well as an electromagnetic parametric study. These developments were validated first experimentally with the measurement of polystyrene beads, which present a simplified dielectric model compared to the complexity of a biological cell, followed then by living individual cells in their culture medium. The test bench was also optimized to allow the dielectric measurement of cells over time, and especially in response to a chemical stimulus. The reaction kinetics of a single-cell subjected to saponin was recorded automatically for different cells. This work opens the door to single-cell analysis with microwave dielectric spectroscopy of complex biological processes in real-time
Mascalchi, Patrice. "Analyse par suivi de particule unique à la surface de lymphocytes vivants de l'organisation dynamique des récepteurs CD4 et CCR5 impliqués dans l'infection par le VIH". Toulouse 3, 2012. http://thesesups.ups-tlse.fr/1560/.
Texto completoInfection of CD4+ T lymphocytes by the human immunodeficiency virus (HIV) is initiated by the sequential interaction of the viral envelope protein gp120 with the primary receptor CD4 and then a coreceptor, CCR5 in most cases of primo-infection. The necessity of this double interaction suggests that the efficiency of the HIV entry process could depend on the dynamic membrane organization of these two receptors. To study this organization at the surface of living lymphocytes, we used single particle tracking (SPT), a high resolution and non-invasive microscopy approach. Firstly, we validated the choice of Quantum dots (QD) for SPT experiments based on the results of a systematic study that evaluated the influence of the particle on the measured diffusion coefficient. Secondly, we determined and analyzed the movement of CD4 and CCR5 receptors labeled with QD, at the surface of lymphocytes immobilized on glass coverslips. These experiments showed that both receptors exhibit three different diffusion modes: random, permanently or transiently confined diffusion. Addition of molecules that destabilize the CD4-CCR5 interaction (soluble CD4, maraviroc) revealed that it is partially responsible for their confinement. All these observations allow us to establish the basis for a model of the dynamic membrane organization of CD4 and CCR5 at the surface of living lymphocytes. These data represent a starting-point for the understanding of the presumed relationship between the dynamic organization of the receptors and the first steps of the HIV infection process
Soule, Pierre. "Etude des mécanismes de translocation des peptides pénétrateurs de cellules (cpp) à l'aide de techniques biophysiques". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066563/document.
Texto completoGene therapy relies on an efficient and specific delivery of drugs into targeted cells. For this purpose, the use of carriers that will help the drugs to cross the membrane, without introducing deleterious effect due to the membrane disruption, are promising. A family of such carriers is known as Cell Penetrating Peptides (CPPs). These peptides are short, about ten amino acids, and often cationic. They are able to translocate through the membrane with different cargos and deliver them into the cytosol. However the mechanisms are still, to a great extent, unknown. We used three biophysical techniques to gain insights into the mechanisms leading to the translocation of a CPP. i) We found the heparan sulfates to be the strongest partner of the CPP penetratin at the cell surface. This adhesion has been pointed out using the Biomembrane Force Probe, a force measuring tool. ii) We evidenced the translocation of penetratin through the lipid bilayer (without any cell mechanism) as long as it contains enough negatively charged lipids. This has been carried out using model bilayers formed at the interface between droplets generated by an inverted emulsion: water in an oil and lipid mixture. iii) To view the translocation of CPPs at the single molecule level we developed a total internal reflection fluorescence microscope (TIRFM) on a suspended bilayer
SION, BENOIT. "Etudes dynamiques de la liberation du gp87 (secretogranine ii) par les cellules hypophysaires de rat in vitro". Rennes 1, 1991. http://www.theses.fr/1991REN10129.
Texto completoBaker, Aurélie. "Etude, à la surface de cellules vivantes, des changements de compartimentation latérale et de co-localisation dynamique du CD4 et du co-récepteur CCR5 au VIH". Toulouse 3, 2007. http://thesesups.ups-tlse.fr/177/.
Texto completoData on dynamic and membrane organization of receptors are still incomplete, and a thorough analysis of the dynamic behaviour of the HIV co-receptors within the membrane is needed for a better understanding of the early steps of the infection process. To investigate the diffusion behavior of CD4 and CCR5 in the membrane of living HEK293T cells, we used two biophysical approaches: vrFRAP and SPT. These techniques allow on the one hand, a membrane domain characterization and on the other hand a dynamical study of the lateral diffusion of the receptors inside this domains. The use in parallel of vrFRAP and SPT, on living cell, gives access on the collective (vrFRAP) and individual (SPT) diffusion behaviour of the receptors. Four stable monoclonal cell lines, expressing CD4 and/or CCR5, were established. Experiments carry out on theses cell lines show further evidence for a specific interaction between CD4 and CCR5 receptors at the basal state and demonstrate that these interactions involved several CCR5 per CD4. Finally, for the first time, we highlight the dynamics of this prefusion complex within the membrane of living cells and our results allow us to propose a schematic model of the membrane organization of the co-expressed receptors CD4 and CCR5
Laplatine, Loïc. "Résolution spatiale en microscopie par résonance de plasmon de surface à couplage par prisme". Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENY044/document.
Texto completoPrism-based surface plasmon resonance (SPR) microscopy is an optical imaging technique invented in the late 60s'. Its main advantage lies in its high sensitivity to optical index or thickness variations at a metal surface. Therefore, the monitoring of biological reactions can be performed in real-time without labeling agent such as fluorescence or enzymes. Over the last 30 years, SPR microscopy has become the major technique in label-free biodetection. The field of application range from the determination of affinity constant in biochemistry to the detection of pathogenic bacteria via cellular biology. Until now, the propagation length of the surface plasmons has been considered as the spatial resolution limit. However, many examples do not support this statement. In this PhD thesis, we demonstrate that the resolution is also limited by optical aberrations induced by the prism used to couple light and surface plasmons. Thus, we are able to explain why the experimental resolution was usually worse than the predicted one. The analysis of the image formation and the quantification of aberrations lead us to suggest two new optical configurations optimized for resolution. We also analyze which metal exhibits the better trade-off between propagation length and sensitivity. Experimentally, we obtain a resolution between 1.5 and 4 μm depending on the direction, on field-of-view up to several mm2, and with a standard sensitivity for biodetection (monolayer of DNA). We are then able to observe simultaneously several thousands of individual eukaryote and prokaryote cells. Finally, we develop a prototype dedicated to the real-time monitoring of protein secretion by immune cells. The limits of SPR microscopy and the solutions which could allow this kind of study are discussed. Preliminary results on the improvement of bacterial detection are also presented
Deguine, Jacques. "Dynamiques cellulaires de l'activité cytotoxique des cellules Natural Killer et T CD8+ au cours de réponse immunitaires anti-tumorales". Paris 7, 2011. http://www.theses.fr/2011PA077237.
Texto completoNatural Killer (NK) and CD8+ T cells, respectively of the innate and adaptive immune System, can both participate in tumor cell lysis through the exocytosis of lytic granules during interactions with their targets. However, while CD8+ T cells are specific for given tumor antigens, NK cells more broadly recognize stress through receptors such as NKG2D, whose ligands are expressed upon cellular stress. To understand how NKG2D receptor engagement influences intratumoral NK cell dynamics, we performed intravital two-photon imaging on solid EL4 tumors expressing the ligand Rae-lp. Expression of this ligand induced a sharp increase in intratumoral NK cell density and motility, whereas only a few immotile NK cells could be observed within a control EL4 tumor. Strinkingly, most NK cells established transient contacts with EL4 Rae-ß tumor cells, while CD8+ T cells interactions with related tumor cells expressing a recognized antigen were stable and long-lasting. We also performed in vitro conjugation experiments to characterize the underlying mechanism of NK and CD8+ T cell behavior and found that while NK cells can eliminate their targets efficiently, their adhesion to targets and the calcium influx during this process were limited. On the other hand, T cell conjugation to a tumor cell expressing a specific antigen induced a robust calcium influx that was critical for the strong adhesion. Altogether, we demonstrate here that while NK and CD8+ T cells use the same molecular effectors during cytotoxicity, they do so with remarkably distinct dynamics. These different behaviors might open the way to immunotherapeutic strategies exploiting the potential synergy of these two cell types
Tounsi, Rami. "Comportement des structures en nids d'abeilles sous sollicitations dynamiques mixtes compression/cisaillement et effet de l'orientation des cellules". Phd thesis, Université de Valenciennes et du Hainaut-Cambresis, 2014. http://tel.archives-ouvertes.fr/tel-01002421.
Texto completoOrduz, Pérez David Andrés. "Propriétés électrophysiologiques des synapses Purkinje-Purkinje du cervelet de souris et caractérisation des dynamiques calciques des boutons présynaptiques de leurs collatérales récurrentes". Paris 6, 2007. http://www.theses.fr/2007PA066247.
Texto completoHostein, Richard. "Étude des propriétés optiques et dynamiques des boîtes quantiques InAsP/InP(001); Application à la réalisation de sources de photons uniques et lasers à cristaux photoniques émettant à 1.5 µm". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2009. http://tel.archives-ouvertes.fr/tel-00439577.
Texto completoEl, Beheiry Mohamed Hossam. "Towards whole-cell mapping of single-molecule dynamics". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066618/document.
Texto completoImaging of single molecules inside living cells confers insight to biological function at its most granular level. Single molecules experience a nanoscopic environment that is complicated, and in general, poorly understood. The modality of choice for probing this environment is live-cell localisation microscopy, where trajectories of single molecules can be captured. For many years, the great stumbling block in comprehension of physical processes at this scale was the lack of information accessible; statistical significance and robust assertions are hardly possible from a few dozen trajectories. It is the onset of high-density single-particle tracking that has dramatically reframed the possibilities of such studies. Importantly, the consequential amounts of data it provides invites the use of powerful statistical tools that assign probabilistic descriptions to experimental observations. In this thesis, Bayesian inference tools have been developed to elucidate the behaviour of single molecules via the mapping of motion parameters. As a readout, maps describe heterogeneities at local and whole-cell scales. Importantly, they grant quantitative details into basic cellular processes. This thesis uses the mapping approach to study receptor-scaffold interactions inside neurons and non-neuronal cells. A promising system in which interactions are patterned is also examined. It is shown that interactions of different types of chimeric glycine receptors to the gephyrin scaffold protein may be described and distinguished in situ. Finally, the prospects of whole-cell mapping in three-dimensions are evaluated based on a discussion of state-of-the-art volumetric microscopy techniques
Phung-Koskas, Thu. "Microtubules stables et microtubules dynamiques dans les cellules hépatiques : aspects structuraux et implications dans la voie de signalisation de l'hormone de croissance". Paris 11, 2002. http://www.theses.fr/2002PA114825.
Texto completoPichené, Matthieu. "Analyse multi-niveaux en biologie systémique computationnelle : le cas des cellules HeLa sous traitement apoptotique". Thesis, Rennes 1, 2018. http://www.theses.fr/2018REN1S026/document.
Texto completoThis thesis examines a new way to study the impact of a given pathway on the dynamics of a tissue through Multi-Level Analysis. The analysis is split in two main parts: The first part considers models describing the pathway at the cellular level. Using these models, one can compute in a tractable manner the dynamics of a group of cells, representing it by a multivariate distribution over concentrations of key molecules. % of the distribution of the states of this pathway through groups of cells. The second part proposes a 3d model of tissular growth that considers the population of cell as a set of subpopulations, partitionned such as each subpopulation shares the same external conditions. For each subpopulation, the tractable model presented in the first part can be used. This thesis focuses mainly on the first part, whereas a chapter covers a draft of a model for the second part
Jaffredo, Manon. "Communications intercellulaires dynamiques au sein des îlots pancréatiques analysées par multi-electrode arrays : rôles physiologiques et applications biotechnologiques en diabétologie". Thesis, Bordeaux, 2021. http://www.theses.fr/2021BORD0120.
Texto completoPancreatic islets are the main sensor of glycaemia and they integrate all the metabolic and hormonal inputs to adapt in real time the secretion of hormones such as insulin by β cells and glucagon by α cells. In type 1 diabetes (T1D) β cells are destroyed by immune attack, and in T2D, β cell mass, function and the intra-islet network are altered. The islet micro-organs are highly reactive due to their electrical properties encoding rapid information and due to intercellular communications between β cells and β/non-β cells. Nevertheless, non-invasive, high resolution and long-term approaches for analysis are still lacking. Extracellular electrophysiology with multi-electrode arrays (MEAs) allows this analysis of islets by measuring both cellular as well as multicellular signals (SPs) due to β cell coupling. During my PhD, I used MEAs (i) to explore islet physiology/pathophysiology and (ii) for biotechnological applications in diabetology. I have shown that biphasic kinetics of insulin secretion are encoded by SPs through dynamic changes in β cell coupling. An important intestinal hormone (GLP-1) increases the 2nd phase of β-cell activity while diabetic conditions (glucotoxicity) reduce the 1st phase. Islet responses to nutrients also require α/β cell cooperation since α cell ablation in the inducible GluDTR mice model reduced both the basal and 2nd phase of β cell activity generated by glucose and a physiological mix of amino acids. I have also performed the electrophysiological characterization of human β cells derived from induced pluripotent stem cells (iPSC), determined their coupling, established their quality control and shown the functional impact of a mutation of interest (ZnT8) edited by CRISPR/Cas9. A functional quality control of human islets prior to transplantation in T1D patients was also performed for correlations with clinical data. Finally, my SP recordings analyzed in real time by microelectronics has contributed to validate an in silico model of biosensor in a FDA-approved simulator of T1D patients. In conclusion, my work demonstrates (i) the role of intra-islet communications in the dynamic physiological adaptation of these micro-organs, (ii) and that detailed characterization of SPs opens new applications from artificial pancreas to personalized cell therapy
Pagliaro, Sarah Beatriz De Oliveira. "Transcriptional control induced by bcr-abl and its role in leukemic stem cell heterogeneity. Single-Cell Transcriptome in Chronic Myeloid Leukemia: Pseudotime Analysis Reveals Evidence of Embryonic and Transitional Stem Cell States Single Cell Transcriptome in Chronic Myeloid Leukemia (CML): Pseudotime Analysis Reveals a Rare Population with Embryonic Stem Cell Features and Druggable Intricated Transitional Stem Cell States A novel neuronal organoid model mimicking glioblastoma (GBM) features from induced pluripotent stem cells (iPSC) Experimental and integrative analyses identify an ETS1 network downstream of BCR-ABL in chronic myeloid leukemia (CML)". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASQ032.
Texto completoChronic myeloid leukemia is a clonal hematopoietic malignancy, characterized by the acquisition of the t (9;22) translocation leading to Ph1 chromosome and its counterpart BCR-ABL oncogene, in a very primitive hematopoietic stem cell. CML is a model of targeted therapies as the proof of concept of the feasibility of targeting the tyrosine kinase (TK) activity BCR-ABL using TK inhibitors (TKI) has been shown to lead to major responses and remissions. However, the current problems encountered in these therapies are primitive leukemic stem cells resistance and their persistence which is thought to be related to the heterogeneity of the stem cells at diagnosis leading to clonal selection of cells resisting to TKI therapies. I have applied the technology of single cell transcriptome analysis to CML cells using a panel of genes involved in different pathways combined with trajectory inference analysis to the gene expression pattern. The results showed a transitional stem cell states including embryonic genes identified in CML cells at diagnosis which could contribute to LSC resistance and persistence. Furthermore, the oncoprotein Bcr-Abl is the constitutively active tyrosine kinase produced by the chimeric BCR-ABL gene in chronic myeloid leukemia (CML). The transcriptional targets of Bcr-Abl in leukemic cells have not been extensively studied. A transcriptome experiment using the hematopoietic UT7 cell line expressing BCR-ABL, has identified the overexpression of eukaryotic elongation factor kinase 2 (eEF2K) which plays a major role in the survival of cells upon nutrient deprivation. Overall, the data suggest that overexpression of eEF2K in CML is associated with an increased sensitivity to nutrient-deprivation
Menneson, Eric. "TRANSPORT TRANSENDOTHÉLIAL DE GÈNES : ÉTUDES DYNAMIQUES DU PASSAGE SÉLECTIF DE POLYPLEXES AU TRAVERS DE L'ENDOTHÉLIUM VASCULAIRE PULMONAIRE". Phd thesis, Université d'Orléans, 2005. http://tel.archives-ouvertes.fr/tel-00011964.
Texto completoCarabana, Garcia Claudia. "Defining cell fate specification of mouse Mammary Stem Cells in 4D". Electronic Thesis or Diss., Université Paris sciences et lettres, 2022. http://www.theses.fr/2022UPSLS055.
Texto completoDEFINING CELL FATE SPECIFICATION OF MOUSE MAMMARY STEM CELLS IN 4DCoordination of cell fate specification and branching morphogenesis is necessary to generate an organ with its specialized final structure and function. Accordingly, how different cell types are specified in a tightly regulated manner in time and space, in order to drive the morphogenesis of a complex tissue, remains a major question in the field of developmental biology.The mammary gland (MG) consists in a branched bi-layered epithelium composed of an outer layer of basal cells (BCs) and an inner compartment of polarised luminal cells (LCs). In this tissue, adult homeostasis is exclusively maintained by lineage-restricted unipotent progenitors, whereas multipotent mammary stem cells (MaSCs) are only found in the embryonic gland, making it an ideal tissue paradigm to study stem cell dynamics and lineage specification, as well as their contribution to tissue morphogenesis.WORKING HYPOTHESISOur recent results showed that multipotent MaSCs become lineage-restricted around embryonic day E15.5, coinciding with the first morphogenetic events that establish the mammary ductal network. We thus hypothesized that loss of multipotency in the mammary gland was linked to cell rearrangements, leading to the branching of embryonic mammary buds. However, the exact timing and the mechanisms responsible for the switch from multipotency to unipotency during embryonic MG are still unknown.AIM AND METHODOLOGYThe overarching aim of this project was to characterise the stem cell dynamics underlying MaSCs differentiation during MG development, and to define the transcriptional signals underpinning this process. We have approached this ambitious objective combining two approaches: 1) single-cell RNA sequencing analysis at different embryonic times, to discover which signals determine cell identity during mammary development, and 2) a live lineage tracing approach in ex vivo embryonic mammary cultures to study dynamic cell behaviours and rearrangements during the earliest phases of mammary growth.RESULTSWe found that lineage restriction is a progressive developmental process. By single cell transcriptomics, we identified a single population of mammary epithelial cells at E13.5, but we could distinguish three transcriptionally distinct cell subsets at E15.5, which included luminal-like, basal-like and hybrid cells co-expressing luminal and basal genes. Spatial transcriptomic analysis revealed that the basal-like and luminal-like clusters were indeed already spatially restricted in the embryonic mammary bud, being positioned either in close proximity to the basement membrane or in the inner bud region, respectively. Importantly, this analysis revealed novel molecular markers of committing LCs and BCs, that cannot be distinguished with known adult MG markers.Additionally, we report the transcriptional signatures distinguishing two spatially restricted embryonic mammary mesenchymal cell populations, representing sub-epithelial and dermal mesenchyme. Long-term live-imaging revealed that paracrine signalling from embryonic mesenchyme to epithelial cells, via Fgf10-Fgfr2, influences epithelial branching.We then developed a deep learning-based pipeline to semi-automatically track individual cells and tissue branches in embryonic mammary explants analysed by time-lapse microscopy. We show that the initial steps of morphogenesis are characterized by highly dynamic cell rearrangements in the growing branch tips. However, forced activation of the Wnt/b-catenin pathway in the embryonic mammary epithelium precluded branching in vivo and ex vivo, indicating that epithelial Wnt signalling is an essential regulator of mammary branching morphogenesis.This work sheds light on the timing and mechanisms governing mammary cell fate decisions, providing potential biomarkers of breast cancer, which often arises from reactivation of embryonic multipotency programs
Madrid, Canales Ignacio. "Model of Cellular Growth under Stress : Emergence of Heterogeneity and Impact of the Environment". Electronic Thesis or Diss., Institut polytechnique de Paris, 2024. http://www.theses.fr/2024IPPAX008.
Texto completoThis thesis focuses on understanding individual-scale cell growth under stress. Starting from the analysis of the data collected by Sebastián Jaramillo and James Broughton under the supervision of Meriem El Karoui, we have developed various models to comprehend the impact of the heterogeneous response to genotoxic stress (SOS response) on the growth of a Escherichia coli populations. We employ measure-values stochastic processes to model the dynamics of these populations.Firstly, we construct a stochastic model based on the "adder" size-control model, extended to incorporate the dynamics of the SOS response and its effect on cell division. The chosen framework is parametric, and the model is fitted by maximum likelihood to individual lineage data obtained in mother machine. This allows us to quantitatively compare inferred parameters in different environments.Next, we explore the ergodic properties of a more general model than the "adder," addressing open questions about its long-time behaviour. We consider a general deterministic flow and a fragmentation kernel that is not necessarily self-similar. We demonstrate the existence of eigenelements. Then, a Doob dollar_h_dollar-transform with the found eigenfunction reduces the problem to the study of a conservative process. Finally, by proving a "petite set" property for the compact sets of the state space, we obtain the exponential convergence.Finally, we consider a bitype age-structured model capturing the phenotypic plasticity observed in the stress response. We study the survival probability of the population and the population growth rate in constant and periodic environments. We evince a trade-off for population establishment, as well as a sensitivity with respect to the model parameters that differs for survival probability and growth rate.We conclude with an independent section, collaborative work initiated during CEMRACS 2022. We investigate numerically the spatial propagation of size-structured populations modeling the collective movement of Myxobacteria clusters via a system of reaction-diffusion equations
Dos, Santos Ferreira Jorge. "Identification des mécanismes en boucle fermée dans le comportement cellulaire". Compiègne, 2008. http://www.theses.fr/2008COMP1734.
Texto completoThe aim of this work is to try to use observed global changes to understand interactions between individual nodes inside biochemical networks. We have worked on the determination of the essential interactions in the auto regulatory process that describes the cell cycle of Xenopus frog eggs. The results make possible an assessment of the effect of each protein on the biochemical network stability. The technique was applied also to a dynamical analysis of a uterine cell electrical activity model with view to study the impact of physiological parameters on the response of the model and identify the main subsystems generating the electrical activity. We also present a model developed for understanding an enzymatic diffusion-reaction system. The objective is to analyze the dynamic behavior of three different chemical species, the modification of enzymatic kinetic properties and the existence of sophisticated behaviors resulting of the catalytic activity induced by immobilization of Acetylcholinesterase enzyme into an artificial membrane enzymatically inactive. The results make possible the characterization and prediction of system behavior as well as a qualitative analysis of the system stability via bifurcation diagrams. The model is then extrapolated to a distributed system in order to analyze its spatio-temporal behavior. Numerical results make possible the assessment of the concentration profile of the chemical species on space and time, what is not directly observable by biochemists. Finally, we study a model developed for a network of Sinorhizobium meliloti bacterium and propose an algorithm for intracellular fluxes estimation
Terry, Emmanuelle. "Modélisation mathématique des dynamiques de la réponse immunitaire T CD8, aux échelles cellulaire et moléculaire". Phd thesis, Université Claude Bernard - Lyon I, 2012. http://tel.archives-ouvertes.fr/tel-00763897.
Texto completoWoringer, Maxime. "Tools to analyze single-particle tracking data in mammalian cells". Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS419.
Texto completoThis work aims at providing tools to dissect the regulation of transcription in eukaryotic cells, with a focus on single-particle tracking of transcription factors in mammalian cells. The nucleus of an eukeryotic cell is an extremely complex medium, that contains a high concentration of macromolecules (DNA, RNA, proteins) and other small molecules (ATP, etc). How these molecules interact with transcription factors, and thus influence transcription rates is an area of intense investigations. Although some of these interactions can be captured by regular biochemistry, many of them, including weak, non-covalent interactions remain undetected by these methods. Live-cell imaging and single-particle tracking (SPT) techniques are increasingly used to characterize such effects. The inference of biophysical parameters of a given transcription factor (TF), such as its diffusion constant, the number of subpopulations or its residence time on DNA, are crucial to understanding how TF dynamics and transcription intertwine. Accurate and validated SPT analysis tools are needed. To be used by the community, SPT tools should not only be carefully validated, but also be easily accessible to non-programmers. They should also be designed to take into account known biases of the imaging techniques. In this work, we first propose a tool, accessible through a web interface, based on the modeling of the diffusion propagator. We validate it extensively and show that it exhibits state-of-the art performance. We apply this tool to two experimental settings: (1) the study of catalysis-enhanced diffusion in-vitro and (2) the analysis of the dynamics of the c-Myc transcription factor in mammalian cells
Maroc, Nicolas. "Aspects moléculaires, cellulaires et dynamiques du contrôle de l'hématopoïèse et implication pathologique des facteurs de croissance hématopoïétique et de leurs récepteurs : autocrinie des cellules leucémiques et analyse fonctionnelle des récepteurs hématopoïétiques à activité tyrosine kinase". Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX22040.
Texto completoLadjimi, Mohamed Tahar. "Modélisation biophysique de la mort cellulaire en réponse au stress thermique". Thesis, Lille 1, 2019. http://www.theses.fr/2019LIL1R029/document.
Texto completoThe living cell is constantly exposed to various types of stress that can damage its components. When the induced damages are detected, defense mechanisms are activated to repair them while optimally managing the energy resources available and necessary for cell function. If the stress is too severe and the system can not defend itself, death will be inevitable. The cellular response to stress is orchestrated by intracellular signaling networks that are extraordinarily complex. The molecular species constituting these networks perform various tasks through biochemical reactions, forming synchronized biological process machineries. Our approach in this thesis for the study of these networks is to model them mathematically to reproduce an observed phenomenon and identify its key players, analyze their reactions in response to different signals, and possibly make precise enough and experimentally verifiable predictions that can be of an extreme utility for therapeutic applications. In our studies, we focus on thermal stress and on the resulting cellular response in terms of the dynamics of the molecular species involved, but also of cell fate (death or survival) at the end of the exposure, we adress those questions by dynamic models describing the biochemical kinetics of system variables as a consequence of temperature variation. In a first step, we demonstrate through simulations, followed by experimental validation, that the temporal form of heat stress significantly impacts cell survival. This first result highlights a mechanism of saturation of the repair species as a consequence of exposure to high temperatures. In a second step, we study the potential correlation between a variability introduced on the levels of two proteins in the heat shock response network and the phenomenon of fractional killing. According to our model predictions, experimentally measured chaperone proteins (repair species) variability alone is not sufficient to explain fractional killing, which must involve other sources of variability. Finally, an analysis of the isoeffect curves generated by a generic model of the cellular response to transient stress shows the existence of four sensitivity regimes depending on the duration-intensity parameters of the stress as well as on the parameters of the response network and its time scales. Our work highlights the potential and utility of dynamic network models in the characterization of dose-response curves
Causse, Sébastien. "Etude de la dynamique d'activation de la transcription des gènes par l'ARN Polymerase2". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2011. http://tel.archives-ouvertes.fr/tel-00824828.
Texto completoGoetz, Jacky. "Rôle du treillis Mgat5/galectine-3 et de la cavéoline-1 dans la fibrillogenèse de la fibronectine et la migration cellulaire : lien avec la dynamique des points focaux d'adhésion". Thèse, Université Louis Pasteur (Strasbourg) (1971-2008), 2007. http://hdl.handle.net/1866/6702.
Texto completoLadjimi, Mohamed Tahar. "Modélisation biophysique de la mort cellulaire en réponse au stress thermique". Electronic Thesis or Diss., Université de Lille (2018-2021), 2019. http://www.theses.fr/2019LILUR029.
Texto completoThe living cell is constantly exposed to various types of stress that can damage its components. When the induced damages are detected, defense mechanisms are activated to repair them while optimally managing the energy resources available and necessary for cell function. If the stress is too severe and the system can not defend itself, death will be inevitable. The cellular response to stress is orchestrated by intracellular signaling networks that are extraordinarily complex. The molecular species constituting these networks perform various tasks through biochemical reactions, forming synchronized biological process machineries. Our approach in this thesis for the study of these networks is to model them mathematically to reproduce an observed phenomenon and identify its key players, analyze their reactions in response to different signals, and possibly make precise enough and experimentally verifiable predictions that can be of an extreme utility for therapeutic applications. In our studies, we focus on thermal stress and on the resulting cellular response in terms of the dynamics of the molecular species involved, but also of cell fate (death or survival) at the end of the exposure, we adress those questions by dynamic models describing the biochemical kinetics of system variables as a consequence of temperature variation. In a first step, we demonstrate through simulations, followed by experimental validation, that the temporal form of heat stress significantly impacts cell survival. This first result highlights a mechanism of saturation of the repair species as a consequence of exposure to high temperatures. In a second step, we study the potential correlation between a variability introduced on the levels of two proteins in the heat shock response network and the phenomenon of fractional killing. According to our model predictions, experimentally measured chaperone proteins (repair species) variability alone is not sufficient to explain fractional killing, which must involve other sources of variability. Finally, an analysis of the isoeffect curves generated by a generic model of the cellular response to transient stress shows the existence of four sensitivity regimes depending on the duration-intensity parameters of the stress as well as on the parameters of the response network and its time scales. Our work highlights the potential and utility of dynamic network models in the characterization of dose-response curves