Thematische Bibliographien / Hematopoietic stem and progenitor cell

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Auswahl der wissenschaftlichen Literatur zum Thema „Hematopoietic stem and progenitor cell“

Autor: Grafiati

Veröffentlicht am 28. Juni 2021

Zuletzt aktualisiert am 13. Februar 2022

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Zeitschriftenartikel zum Thema "Hematopoietic stem and progenitor cell"

Camargo, Fernando D. „In vivo Stem Cell Clonal Dynamics“. Blood 126, Nr. 23 (03.12.2015): SCI—40—SCI—40. http://dx.doi.org/10.1182/blood.v126.23.sci-40.sci-40.

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Abstract Tremendous progress has been achieved in the characterization of the hematopoietic system over the past two decades. Historically, the main experimental approach used to elucidate and define these cellular relationships in the bone marrow (BM) has been the transplantation assay. For this reason, most of our knowledge about the in vivo properties of hematopoietic stem cells (HSCs) and progenitor cells has been derived from studies in the transplant context. Because of the lack of tractable systems, the mechanistic nature of non-transplant hematopoiesis has remained largely unexplored. Over the past several years, my laboratory has developed novel genetic tools for the clonal tracing and imaging of hematopoietic populations in the unperturbed niche that aim to bring insight into the biology of stem and progenitor cells in situ. Our work using a transposon-mediated cellular tagging approach indicated that progenitors, and not the classical long-term HSCs, are the cells mainly responsible for the day-to-day production of blood cells in the adult. Our data also suggested that lineage restricted progenitors are the main contributors to hematopoiesis at steady state. These data represent the first systematic analysis of clonal fate in an unperturbed hematopoietic niche and revealed a novel cellular mechanism for homeostatic blood regeneration. We have now utilized this clonal tracing model to bring insight into the dynamics of stem and progenitor biology during embryonic hematopoiesis and in the severely aged hematopoietic system. These data will be discussed at the meeting. Disclosures Camargo: Cell Signaling Technologies: Consultancy; Vital Therapies: Consultancy.

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Li, June, Daniel P. Sejas und Qishen Pang. „Nucleophosmin Regulates Differentiation, Cell Cycle Progression, and Stress Response in Hematopoietic Progenitor Cells.“ Blood 106, Nr. 11 (16.11.2005): 312. http://dx.doi.org/10.1182/blood.v106.11.312.312.

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Abstract Nucleophosmin (NPM) is a multifunctional protein frequently overexpressed in actively proliferating cells including tumor and hematopoietic stem cells. Strong evidence indicates that NPM is involved in hematopoiesis and leukemic development. Here we report that NPM enhances the proliferative potential of hematopoietic stem/progenitor cells and increases cell survival upon stress challenge. Specifically, lin-Sca1+c-kit+ bone marrow cells transduced with retroviral vector expressing NPM exhibited higher proliferative rates in both short-term liquid culture and clonogenic progenitor cell assays, compared to the cells transduced with empty vector. Interestingly, NPM overexpression appears to inhibit differentiation of myeloid progenitors. Hematopoietic stem/progenitor cells infected with the NPM retrovirus expressed significantly lower levels of mature cell markers Gr-1 and Mac-1 compared to empty vector transduced cells, and majority of the NPM-overexpressing cells remained Sca1+C-Kit+ during the 5-day culture. Bone marrow transplantation experiments demonstrated that NPM overexpression increases long-term multi-lineage repopulating capacity of hematopoietic progenitors. We have not observed any evidence of proliferative disorders or leukemia in recipients transplanted with NPM-expressing progenitors thus far (4 months posttransplantation). Through cell-cycle profile analysis and single-cell division experiments, we showed that NPM overexpression induces rapid entry of hematopoietic progenitors into the cell cycle, probably via promoting G0/G1 to S transition. Furthermore, immunocytochemical and Western-blot analyses demonstrated that NPM-transduced cells expressed higher level of cyclin A compared to vector-transduced cells. Finally, overexpression of NPM significantly increased the survival of hematopoietic progenitors exposed to mitomycin C or hydrogen peroxide, suggesting that NPM can protect cells from DNA damage and oxidative stress. Together, these results indicate that NPM plays an important role in hematopoiesis via mechanisms involving modulation of progenitor differentiation, cell cycle progression, and stress response.

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Kristensen, Helene Bjoerg, Thomas Levin Andersen, Andrea Patriarca, Klaus Kallenbach, Birgit MacDonald, Tanja Sikjaer, Charlotte Ejersted und Jean-Marie Delaisse. „Human hematopoietic microenvironments“. PLOS ONE 16, Nr. 4 (20.04.2021): e0250081. http://dx.doi.org/10.1371/journal.pone.0250081.

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Dormancy of hematopoietic stem cells and formation of progenitors are directed by signals that come from the bone marrow microenvironment. Considerable knowledge has been gained on the murine hematopoietic stem cell microenvironment, while less so on the murine progenitor microenvironment and even less so on these microenvironments in humans. Characterization of these microenvironments is decisive for understanding hematopoiesis and finding new treatment modalities against bone marrow malignancies in the clinic. However, it is equally challenging, because hematopoietic stem cells are difficult to detect in the complex bone marrow landscape. In the present study we are characterizing the human hematopoietic stem cell and progenitor microenvironment. We obtained three adjacent bone marrow sections from ten healthy volunteers. One was used to identify a population of CD34+/CD38- “hematopoietic stem cells and multipotent progenitors” and a population of CD34+/CD38+ “progenitors” based on immunofluorescence pattern/intensity and cellular morphology. The other two were immunostained respectively for CD34/CD56 and for CD34/SMA. Using the combined information we performed a non-computer-assisted quantification of nine bone marrow components (adipocytes, megakaryocytes, bone surfaces, four different vessel types (arteries, capillaries, sinusoids and collecting sinuses), other “hematopoietic stem cells and multipotent progenitors” and other “progenitors”) within 30 μm of “hematopoietic stem cells and multipotent progenitors”, “progenitors”, and “random cell profiles”. We show that the microenvironment of the “hematopoietic stem cells and multipotent progenitors” is significantly enriched in sinusoids and megakaryocytes, while the microenvironment of the “progenitors” is significantly enriched in capillaries, other “progenitors”, bone surfaces and arteries.

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Esmaeli-Azad, Babak, Anand S. Srivastava, Cybele Frederico, Geraldo Martinez, Satoshi Yasukawa und Ewa Carrier. „Artificial Hematopoietic Stem Cell Niche Sustains Growth and Differentiation of Human ES-Derived Early Hematopoietic Progenitors.“ Blood 110, Nr. 11 (16.11.2007): 1415. http://dx.doi.org/10.1182/blood.v110.11.1415.1415.

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Abstract Using a novel Microplate Biomaterial Microarray (MBM™) technology, we have created an artificial hematopoietic stem cell niche that can sustain growth and differentiation of human embryonic stem cells-derived (hES) early hematopoietic progenitors. This hydrogel based ex-vivo niche allows uploading of human embryonal stem cells, human mesenchymal stem cells (MSC), genes (bcl-2 preventing apoptosis and HoxB4 enhancing hematopoiesis) and extracellular matrices to support growth and differentiation of human ES cells. These experiments were done using NIH-approved hES cell lines H1 and H9. Serum-free, feeder-free culture conditions were established and early hematopoietic progenitors grown using SCF, TPO, VEGF and IL-3 with high efficiency. At day 3–5 dual CD34+/CD31+ progenitors were identified, while on day 7–8 CD34+ hematopoietic progenitors were isolated, which formed typical hematopoietic colonies. These progenitors expressed genes related to early hematopoiesis, such as TAL1/SCL, FLT1, GATA2, GATA1, EPOR and TPOR. The early dual endothelio-hematopoietic progenitor (hemangioblast) expressed PECAM-1 and CD34 and showed typical blast-like morphology. Based on mathematical simulations, various micro-niches were designed to establish optimal differentiation conditions for this progenitor using IL-3, IL-6, TPO, EPO, VEGF, SFC, Flt-3 ligand and various extracellular matrices. Specific micro-niches were created for generation of CFU-E, BFU-E, CFU-GM, CFU-GEMM, CFU-M, CFU-G, and CFU-MK progenitors from human ES-derived hemangioblast. Kinetic uploading of TPO, EPO, SCF and VEGF created a niche-sustaining growth of ES-derived hemangioblast with high efficiency and low apoptosis rate. These niches used pulse -delivery of anti-apoptotic bcl-2 gene and hematopoiesis-enhancing Hoxb4 gene. The model of artifical niche sustaing growth and differentiation of human ES-derived hemangioblast was established. In the future, this system will allow optimized and upscaled generation of early hematopoietic progenitors from human ES cells, as a first step towards clinical applications of human embryonic stem cells. Figure Figure

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Cheng, J., S. Baumhueter, G. Cacalano, K. Carver-Moore, H. Thibodeaux, R. Thomas, HE Broxmeyer et al. „Hematopoietic defects in mice lacking the sialomucin CD34“. Blood 87, Nr. 2 (15.01.1996): 479–90. http://dx.doi.org/10.1182/blood.v87.2.479.bloodjournal872479.

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Although the pluripotent hematopoietic stem cell can only be definitively identified by its ability to reconstitute the various mature blood lineages, a diversity of cell surface antigens have also been specifically recognized on this subset of hematopoietic progenitors. One such stem cell-associated antigen is the sialomucin CD34, a highly O-glycosylated cell surface glycoprotein that has also been shown to be expressed on all vascular endothelial cells throughout murine embryogenesis as well as in the adult. The functional significance of CD34 expression on hematopoietic progenitor cells and developing blood vessels is unknown. To analyze the involvement of CD34 in hematopoiesis, we have produced both embryonic stem (ES) cells and mice that are null for the expression of this mucin. Analysis of yolk saclike hematopoietic development in embryoid bodies derived from CD34- null ES cells showed a significant delay in both erythroid and myeloid differentiation that could be reversed by transfection of the mutant ES cells with CD34 constructs expressing either a complete or truncated cytoplasmic domain. Measurements of colony-forming activity of hematopoietic progenitor cells derived from yolk sacs or fetal livers isolated from CD34-null embryos also showed a decreased number of these precursor cells. In spite of these diminished embryonic hematopoietic progenitor numbers, the CD34-null mice developed normally, and the hematopoietic profile of adult blood appeared typical. However, the colony-forming activity of hematopoietic progenitors derived from both bone marrow and spleen is significantly reduced in adult CD34-deficient animals, and these CD34-deficient progenitors also appear to be unable to expand in liquid cultures in response to hematopoietic growth factors. Even with these apparent progenitor cell deficiencies, CD34- null animals showed kinetics of erythroid, myeloid, and platelet recovery after sublethal irradiation that are indistinguishable from wild-type mice. These data strongly suggest that CD34 plays an important role in the formation of progenitor cells during both embryonic and adult hematopoiesis. However, the hematopoietic sites of adult CD34-deficient mice may still have a significant reservoir of progenitor cells that allows for normal recovery after nonmyeloablative peripheral cell depletion.

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Upadhaya, Samik, Catherine M. Sawai, Efthymia Papalexi, Ali Rashidfarrokhi, Geunhyo Jang, Pratip Chattopadhyay, Rahul Satija und Boris Reizis. „Kinetics of adult hematopoietic stem cell differentiation in vivo“. Journal of Experimental Medicine 215, Nr. 11 (05.10.2018): 2815–32. http://dx.doi.org/10.1084/jem.20180136.

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Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady-state. Labeled cells, comprising primarily long-term HSCs and some short-term HSCs, produced megakaryocytic lineage progeny within 1 wk in a process that required only two to three cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic, and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 wk of tracing. These results show that continuous differentiation of HSCs rapidly produces major hematopoietic lineages and cell types and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and lymphoid differentiation.

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Woolthuis, Carolien M., und Christopher Y. Park. „Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage“. Blood 127, Nr. 10 (10.03.2016): 1242–48. http://dx.doi.org/10.1182/blood-2015-07-607945.

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Abstract The classical model of hematopoiesis has long held that hematopoietic stem cells (HSCs) sit at the apex of a developmental hierarchy in which HSCs undergo long-term self-renewal while giving rise to cells of all the blood lineages. In this model, self-renewing HSCs progressively lose the capacity for self-renewal as they transit into short-term self-renewing and multipotent progenitor states, with the first major lineage commitment occurring in multipotent progenitors, thus giving rise to progenitors that initiate the myeloid and lymphoid branches of hematopoiesis. Subsequently, within the myeloid lineage, bipotent megakaryocyte-erythrocyte and granulocyte-macrophage progenitors give rise to unipotent progenitors that ultimately give rise to all mature progeny. However, over the past several years, this developmental scheme has been challenged, with the origin of megakaryocyte precursors being one of the most debated subjects. Recent studies have suggested that megakaryocytes can be generated from multiple pathways and that some differentiation pathways do not require transit through a requisite multipotent or bipotent megakaryocyte-erythrocyte progenitor stage. Indeed, some investigators have argued that HSCs contain a subset of cells with biased megakaryocyte potential, with megakaryocytes directly arising from HSCs under steady-state and stress conditions. In this review, we discuss the evidence supporting these nonclassical megakaryocytic differentiation pathways and consider their relative strengths and weaknesses as well as the technical limitations and potential pitfalls in interpreting these studies. Ultimately, such pitfalls will need to be overcome to provide a comprehensive and definitive understanding of megakaryopoiesis.

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Jing, Lili, Owen J. Tamplin, Michael J. Chen, Qing Deng, Shenia Patterson, Peter G. Kim, Ellen M. Durand et al. „Adenosine signaling promotes hematopoietic stem and progenitor cell emergence“. Journal of Experimental Medicine 212, Nr. 5 (13.04.2015): 649–63. http://dx.doi.org/10.1084/jem.20141528.

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Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1+/cmyb+ HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl+ hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP–protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates.

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Mazo, Irina B., Steffen Massberg und Ulrich H. von Andrian. „Hematopoietic stem and progenitor cell trafficking“. Trends in Immunology 32, Nr. 10 (Oktober 2011): 493–503. http://dx.doi.org/10.1016/j.it.2011.06.011.

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Mitjavila-Garcia, Maria Teresa, Michel Cailleret, Isabelle Godin, Maria Manuela Nogueira, Karine Cohen-Solal, Valérie Schiavon, Yann Lecluse, Françoise Le Pesteur, Anne Hélène Lagrue und William Vainchenker. „Expression of CD41 on hematopoietic progenitors derived from embryonic hematopoietic cells“. Development 129, Nr. 8 (15.04.2002): 2003–13. http://dx.doi.org/10.1242/dev.129.8.2003.

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In this study, we have characterized the early steps of hematopoiesis during embryonic stem cell differentiation. The immunophenotype of hematopoietic progenitor cells derived from murine embryonic stem cells was determined using a panel of monoclonal antibodies specific for hematopoietic differentiation antigens. Surprisingly, the CD41 antigen (αIIb integrin, platelet GPIIb), essentially considered to be restricted to megakaryocytes, was found on a large proportion of cells within embryoid bodies although very few megakaryocytes were detected. In clonogenic assays, more than 80% of all progenitors (megakaryocytic, granulo-macrophagic, erythroid and pluripotent) derived from embryoid bodies expressed the CD41 antigen. CD41 was the most reliable marker of early steps of hematopoiesis. However, CD41 remained a differentiation marker because some CD41– cells from embryoid bodies converted to CD41+ hematopoietic progenitors, whereas the inverse switch was not observed. Immunoprecipitation and western blot analysis confirmed that CD41 was present in cells from embryoid bodies associated with CD61 (β3 integrin, platelet GPIIIa) in a complex. Analysis of CD41 expression during ontogeny revealed that most yolk sac and aorta-gonad-mesonephros hematopoietic progenitor cells were also CD41+, whereas only a minority of bone marrow and fetal liver hematopoietic progenitors expressed this antigen. Differences in CD34 expression were also observed: hematopoietic progenitor cells from embryoid bodies, yolk sac and aorta-gonad-mesonephros displayed variable levels of CD34, whereas more than 90% of fetal liver and bone marrow progenitor cells were CD34+. Thus, these results demonstrate that expression of CD41 is associated with early stages of hematopoiesis and is highly regulated during hematopoietic development. Further studies concerning the adhesive properties of hematopoietic cells are required to assess the biological significance of these developmental changes.

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Dissertationen zum Thema "Hematopoietic stem and progenitor cell"

Liu, Yi. „LATEXIN’S ROLE IN REGULATING HEMATOPOIETIC STEM AND PROGENITOR CELLS“. UKnowledge, 2013. http://uknowledge.uky.edu/physiology_etds/11.

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Previous studies in our lab identified a novel gene, latexin (Lxn), that regulates murine hematopoietic stem cells through balancing apoptosis, self-renewal and proliferation. In these dissertation studies, I performed a series of experiments to examine the function of Lxn using a Lxn conventional knockout mouse, and characterize Lxn’s role in the presence of hematopoietic stresses such as ionizing radiation, cytokines induced-mobilization, and hematopoietic malignancy. The first series of experiments was designed to determine the role of Lxn in hematopoiesis under homeostatic conditions. I found that Lxn-/- mice exhibited hyperproliferative hematopoiesis, a repopulation advantage and elevated self-renewal capacity which was intrinsic to the Lxn-/- hematopoietic cells. Furthermore, I identified a reduction in apoptotic frequency in Lxn-/- hematopoietic progenitors, which may account for the expansion seen in the progenitor population. In a second series of experiments, I discovered a role of Lxn in the radio-sensitivity of hematopoietic cells. I found that loss of Lxn in mice confers resistance to ionizing radiation. Lxn-/- mice showed rapid hematological recoveries after radiation exposure at the stem and progenitor cell (HSPC) level. The ablation of Lxn hindered irradiation-induced apoptosis which may underlie the radiation resistance through regulating hematopoietic recovery. In a third series of experiments, I studied the interaction of Lxn-/- stem and progenitor cells with their microenvironment. Using a granulocyte colony-stimulating factor-induced mobilization model, I determined that the ability of HSPCs to mobilize into the bloodstream was significantly increased in Lxn-/- mice. The adhesive properties of hematopoietic cells were compromised in Lxn-/- animals. Gene expression studies on progenitor cells identified cell-to-ECM interactions were down-regulated upon Lxn deletion, implying the enhanced mobilization efficiency of hematopoietic cells from Lxn-/- mice correlated with reduced adhesion of hematopoietic progenitor cells to stroma. Last, but not least, I performed a series of experiments to study the putative tumor suppressor role of Lxn in hematological malignancy. I found that Lxn expression was down-regulated in primary tumor and tumor cell lines by promoter methylation. Overexpression of Lxn inhibited lymphoma cell growth both in vitro and in vivo. Overexpressed Lxn increased apoptosis frequency by suppressing the expression of several anti-apoptotic genes, and therefore reduced the tumor growth.

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Traveset, Martínez Laia 1992. „New insights into transcription that preserve hematopoietic stem cell homeostasis“. Doctoral thesis, Universitat Pompeu Fabra, 2020. http://hdl.handle.net/10803/670105.

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Maintenance of steady-state and stress-adapted hematopoiesis depends on the fitness of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Hematopoietic stem cells (HSCs) can adapt to stress by expanding their numbers and increasing the output of blood cells. This dynamic and highly complex process needs to be fully regulated in order to maintain a balance between the differentiation of HSCs and the need to keep a constant pool of HSCs. However, the molecular machinery in charge of this tight regulation has yet to be fully characterized. HSCs represent a small proportion inside the HSPC compartment, which also includes the immediate progeny of HSCs, the multipotent progenitors (MPP). MPPs are a cell population that retain full lineage potential yet have a limited self-renewal capacity compared to HSC. In this Thesis we explore a novel mechanism important for the maintenance and protection of HSC function under stress. We have characterized HSC homeostasis and function upon serial transplantation, after myeloablative injury and after a protocol of total body irradiation. We present in vivo results elucidating a new transcription mechanism involved in the maintenance of the viability and self-renewal capacity of HSCs that restrains its differentiation to MPPs, in situations in which the hematopoietic system must keep constant the stem cell reservoir in order to avoid HSC exhaustion.
El manteniment de l'hematopoesi en condicions basals i en situacions d’estrès depèn de l'aptitud de les cèl·lules mare i progenitores hematopoètiques (HSPCs) de la medul·la òssia. Les cèl·lules mare hematopoètiques (HSC) són capaces d’adaptar-se a l’estrès mitjançant l'ampliació dels seus nombres i l'augment de la producció de cèl·lules sanguínies. Aquest procés, dinàmic i molt complex, ha d'estar totalment regulat per tal de mantenir un equilibri entre la diferenciació de les HSCs i la necessitat de mantenir un nombre constant de HSCs. No obstant això, la maquinària molecular encarregada d'aquesta regulació no ha estat encara completament caracteritzada. Les HSCs tan sols representen una petita proporció dins del compartiment de HSPCs el qual també inclou la progènie immediata de les HSCs, els progenitors multipotents (MPP). Els MPPs són una població cel·lular que conserva el potencial de llinatge complet, però que presenta una capacitat d'autorenovació limitada en comparació amb les HSCs. En aquesta tesi explorem un nou mecanisme important pel manteniment i la protecció de la funció de les HSCs sota estrès. Hem caracteritzat com la cèl·lula mare hematopoètica funciona després d’un trasplantament en sèrie, després d’una lesió de mielosupressió i després d’un protocol d’irradiació total. Per tant, presentem resultats in vivo que diluciden un nou mecanisme transcripcional implicat en el manteniment de la viabilitat i la capacitat d’autorenovació de les HSC i que restringeix la seva diferenciació cap a MPPs, en situacions en què el sistema hematopoètic ha de mantenir constant el dipòsit de cèl·lules mare per tal d’evitar el seu esgotament.

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Kollek, Matthias [Verfasser], und Miriam [Akademischer Betreuer] Erlacher. „Improvement of hematopoietic stem cell transplantations by transient apoptosis inhibition in donor stem and progenitor cells“. Freiburg : Universität, 2016. http://d-nb.info/1136263462/34.

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Tabayoyong, William Borj. „Engraftment of embryonic stem cell-derived hematopoietic progenitor cells is regulated by natural killer cells“. Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/1089.

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Embryonic stem (ES) cells possess the remarkable ability to form cells and tissues from all three germ layers, a characteristic known as pluripotency. In particular, the generation of ES cell-derived hematopoietic cells could serve as an alternate source of hematopoietic stem cells for transplantation in place of bone marrow cells, which are limited by donor availability and high immunogenicity. The advantages of ES cell-derived hematopoietic cells over bone marrow cells include a greater proliferative capacity, which alleviates the problems of donor shortage, and low level expression of MHC antigens, which suggests immune privilege. However, it is unclear whether the immune system is capable of recognizing and rejecting ES cell-derived hematopoietic cells following transplantation. The observation that ES cell-derivatives express low levels of MHC class I, the predominant inhibitory ligand for NK cells, led us to hypothesize that ES cell-derived hematopoietic progenitor cells (HPC) are susceptible to NK cell-mediated killing. To test this hypothesis, we first generated HPCs from murine ES cells ectopically expressing HOXB4, a homeobox transcription factor that confers hematopoietic self-renewal, and confirmed that HPCs expressed low levels of MHC class I antigens. To specifically investigate the role of NK cells in regulating the in vivo engraftment of HPCs, we transplanted NK-replete Rag2-/- or NK-deficient Rag2-/-γc-/- mice with HPCs. We observed permanent HPC engraftment in Rag2-/-γc-/- mice; however, HPC engraftment was significantly reduced in Rag2-/- mice and was eventually eliminated over time. Bone marrow harvested from these animals showed that HPC-derived Lin-c-kit+ and Lin-Sca-1+ progenitor cells, critical progenitor cells for long-term hematopoietic engraftment, were deleted in Rag2-/- but not in Rag2-/-γc-/- mice. Next, we focused on the mechanism of NK cell activation by HPCs. Increased expression of the cytotoxic proteins Granzyme B and Perforin in the NK cells of HPC-transplanted Rag2-/- mice confirmed in vivo NK cell activation. Phenotypic analysis of HPCs revealed high level expression of H60, a ligand of the NK activating receptor NKG2D, and neutralization of H60 rescued HPCs from NK cell-mediated killing. Altogether, our results demonstrate that NK cells are a major barrier to the successful engraftment of ES cell-derived hematopoietic cells, underlining an important role of the innate immune system in regulating the long-term engraftment of ES cell derivatives.

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Cova, Giovanni. „The role of Helios in the hematopoietic stem and progenitor cell development“. Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ092.

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Les cellules souches et progénitrices hématopoïétiques (CSPH) produisent les cellules sanguines durant toute la vie. Elles sont divisées en cellules souches indifférenciées (CSH) et en cellules progénitrices multipotentes engagées (MPP). Les MPP sont hétérogènes et composées de cellules progénitrices multipotentes engagées vers les lignages érythro-mégacaryocytaires (MPP2), myéloïdes (MPP3) et lymphoïdes (MPP4). Malgré que ces populations cellulaires soient bien définies, les mécanismes moléculaires gouvernants leurs différenciations restent en grande partie encore inconnus. Nous avons montré que le facteur de transcription Hélios, exprimé fortement dans les CSPH, est crucial pour la spécification et le vieillissement des CSPH. Les greffes de moëlle osseuse et les expériences de différenciation ex-vivo et de cytométrie en flux montrent que les souris déficientes pour Hélios possèdent un nombre réduit de MPP4 et de progéniteurs lymphoïdes. Ce déficit est compensé par une augmentation du nombre de MPP3 et de progéniteurs granulo-monocytaires et mégacaryocytaires. De plus l’analyse transcriptionnelle des CSPH indique que la déficience pour Hélios affecte principalement les CSH exprimant des gènes spécifiques aux mégacaryocytes et aux vieilles CSH, tandis que les MPP déficients pour Hélios expriment faiblement les gènes spécifiques aux cellules lymphoïdes. Notre travail montre que Hélios est un nouveau régulateur de la spécification et du vieillissement des HSC
Hematopoietic Stem and Progenitor Cells (HSPC) engender all the mature blood cells throughout life. They are subdivided in undifferentiated stem cells (HSC) and primed multipotent progenitors (MPP). MPP are heterogeneous and composed of erythro-megakaryocytes (MMP2), myeloid (MPP3) and lymphoid (MPP4) primed cells. Despite the fact that these populations are well defined, the molecular mechanisms underlying their differentiation remain unclear. We showed that the transcription factor Helios, highly expressed in the HSPC, is crucial for HSPC specification and aging. Bone marrow transplantation, ex-vivo differentiation and flow cytometry assays revealed that Helios deficient mice have reduced MPP4 as well as lymphoid progenitors. This deficiency is offset by an increase in MPP3, granulo-monocyte and megakaryocyte progenitors. Moreover,transcriptional analysis of HSPC revealed that Helios deficiency affects mainly HSC with an enrichment of megakaryocyte and old HSC genes signatures, where as Helios deficient MPP express lower levels of lymphoid specific genes. Our work reveals Helios as a novel regulator of HSC specification and aging

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Schütte, Judith. „Analysis of regulatory networks in blood stem/progenitor cells“. Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648631.

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Guthrie, Steven Mitchell. „Hemangioblasts from hematopoietic stem cells to endothelial progenitor cells and their effector molecules /“. [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0010068.

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Thesis (Ph.D.)--University of Florida, 2005.
Typescript. Title from title page of source document. Document formatted into pages; contains 95 pages. Includes Vita. Includes bibliographical references.

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Chen, Inn-Inn. „The role of ephrinB2 in hematopoietic stem/progenitor cell differentiation from an arterial hemogenic endothelium“. Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:3a561742-155f-447e-beb6-42ede41d9bb5.

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During development, hematopoiesis develops in temporally distinct waves in the yolk sac (YS) and embryo proper, culminating in the emergence of definitive hematopoietic stem cells (HSCs) from the hemogenic endothelium (HE) of the dorsal aorta. The close association of this aortic endothelium with definitive hematopoiesis suggests a functional relationship between arteriogenesis and blood development, but this association is not fully understood. To gain insight into this relationship, we have chosen to study the role of the “arterial” marker, EphrinB2 (EfnB2) in hematopoietic specification. EfnB2 is a transmembrane protein critical for the development of the arterial vascular system. We find that EfnB2 is expressed in the VE-Cadh⁺CD41^- HE in Day 2 BL-CFC (blast-colony forming cell) culture and Day 6 EBs (embryoid bodies), and that EfnB2 expression in ES cell differentiation enriches for endothelial cells with greater hemogenic capacity. Knock-down experiments in ES cells showed that EfnB2 is not required for endothelial cell commitment and survival. It is also not required for early hematopoietic commitment and differentiation from EBs or BL-CFCs. However, we find that EfnB2 is required for the maturation of ES cells into CD41⁺/CD45⁺ hematopoietic cells in OP9 co-culture and for definitive hematopoietic colony formation in MethoCult3434 medium. This requirement for EfnB2 expression was confirmed by peptide-mediated blocking of EfnB2 binding to its cognate receptors and by forced expression of a phospho-tyrosine signaling-deficient EfnB2. These results provide evidence for an essential role of endothelial EfnB2 in hematopoiesis.

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Eliasson, Pernilla. „Live and Let Die : Critical regulation of survival in normal and malignant hematopoietic stem and progenitor cells“. Doctoral thesis, Linköpings universitet, Experimentell hematologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-52932.

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The hematopoietic stem cell (HSC) is characterized by its ability to self-renew and produce all mature blood cells throughout the life of an organism. This is tightly regulated to maintain a balance between survival, proliferation, and differentiation. The HSCs are located in specialized niches in the bone marrow thought to be low in oxygen, which is suggested to be involved in the regulation of HSC maintenance, proliferation, and migration. However, the importance of hypoxia in the stem cell niche and the molecular mechanisms involved remain fairly undefined. Another important regulator of human HSCs maintenance is the tyrosine kinase receptor FLT3, which triggers survival of HSCs and progenitor cells. Mutations in FLT3 cause constitutively active signaling. This leads to uncontrolled survival and proliferation, which can result in development of acute myeloid leukemia (AML). One of the purposes with this thesis is to investigate how survival, proliferation and self-renewal in normal HSCs are affected by hypoxia. To study this, we used both in vitro and in vivo models with isolated Lineage-Sca-1+Kit+ (LSK) and CD34-Flt3-LSK cells from mouse bone marrow. We found that hypoxia maintained an immature phenotype. In addition, hypoxia decreased proliferation and induced cell cycle arrest, which is the signature of HSCs with long term multipotential capacity. A dormant state of HSCs is suggested to be critical for protecting and preventing depletion of the stem cell pool. Furthermore, we observed that hypoxia rescues HSCs from oxidative stress-induced cell death, implicating that hypoxia is important in the bone marrow niche to limit reactive oxidative species (ROS) production and give life-long protection of HSCs. Another focus in this thesis is to investigate downstream pathways involved in tyrosine kinase inhibitor-induced cell death of primary AML cells and cell lines expressing mutated FLT3. Our results demonstrate an important role of the PI3K/AKT pathway to mediate survival signals from FLT3. We found FoxO3a and its target gene Bim to be key players of apoptosis in cells carrying oncogenic FLT3 after treatment with tyrosine kinase inhibitors. In conclusion, this thesis highlights hypoxic-mediated regulation of normal HSCs maintenance and critical effectors of apoptosis in leukemic cells expressing mutated FLT3.

On the day of the defence date the title of article II was "Hypoxia, via hypoxia-inducible factor (HIF)-1, mediates low cell cycle activity and preserves the engraftment potential of mouse hematopoietic stem cells" and one of the authors is no longer included in the article.

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McBrien, Marie. „The effect of Poly I:C induced inflammation on hematopoietic stem and progenitor cell behaviour in the zebrafish hematopoietic transplant model“. Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/55871.

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Hematopoietic stem cells are a small but significant population of cells fundamental for generating and maintaining the hematopoietic system. These cells are used in the treatment of cancer and auto-immune patients. Studies in mammals suggest that inflammation and infection can modulate the biology of these cells, affecting their location, self-renewal capacity and directing differentiation. The aim of this work was to study the effect of repeated stimulation on the hematopoietic stem and progenitor (HSPCs) population in zebrafish (Danio rerio) to benefit from the live imaging potential of this model organism. It was hypothesised that early post-transplant HSPC behaviour (e.g. lodgement in the niche, self-renewal, mobilisation and differentiation) could be observed and would be indicative of the success or failure of HCT. Double transgenic Tg (cd41:GFP; lysc:dsRed) donors, in which HSPCs express green fluorescent protein (GFP+) and myeloid cells express red fluorescent protein (dsRed+) were used. HSPCs were sorted from donor whole kidney marrow (WKM) and transplanted into irradiated optically-transparent recipients, which were then imaged using wide-field microscopy, individually tracked for survival and hematopoietic reconstitution was assessed after 28 days by flow cytometry. Indeed, initial experiments showed that early observations of cells in the WKM correlated with hematopoietic recovery and survival of recipients, although the strength of the correlation was not sufficiently powerful for predicting recipient outcome. This refinement of the HCT protocol lead to the potentiality of studying the behaviour of HSPCs in the context of inflammation. Inflammation was initiated with repeated intra-peritoneal injections of the viral mimic Polyinosinic:polycytidylic acid (poly I:C) in either the donor or recipient prior to transplant. Poly I:C injection of donors prior to transplant causes HSPCs to colonise the recipient WKM at a greater rate than HSPCs from sham (PBS-injected) donors. However, this did not appear to affect recipient survival or WKM reconstitution at 28 days. Poly I:C injection of recipients prior to transplant did not affect early post-transplant repopulation of the WKM, myelopoiesis, recipient survival, or WKM reconstitution at 28 days. Future work will use competitive transplants to confirm these findings and will explore alternative inflammation models. Furthermore, the confounding factor of irradiation-caused inflammation will be mitigated by transplanting HSPCs into optically-transparent bloodless recipients. Overall, this thesis has demonstrated that the zebrafish can provide valuable in vivo data for studying HSPC behaviour in the recipient post-transplant.

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Chu, Peter Pui Tak. Retroviral-mediated human adenosine deaminase gene transfer into human hematopoietic progenitor and stem cells. Ottawa: National Library of Canada, 1995.

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service), SpringerLink (Online, Hrsg. Hematopoietic Stem Cell Biology. Totowa, NJ: Humana Press, a part of Springer Science+Business Media, LLC, 2010.

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Bishop, Michael R., Hrsg. Hematopoietic Stem Cell Transplantation. Boston, MA: Springer US, 2009. http://dx.doi.org/10.1007/978-0-387-78580-6.

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Godin, Isabelle, und Ana Cumano. Hematopoietic Stem Cell Development. Boston, MA: Springer US, 2006. http://dx.doi.org/10.1007/978-0-387-33535-3.

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Bunting, Kevin D., und Cheng-Kui Qu, Hrsg. Hematopoietic Stem Cell Protocols. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1133-2.

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Soiffer, Robert J., Hrsg. Hematopoietic Stem Cell Transplantation. Totowa, NJ: Humana Press, 2008. http://dx.doi.org/10.1007/978-1-59745-438-4.

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Klug, Christopher A., und Craig T. Jordan. Hematopoietic Stem Cell Protocols. New Jersey: Humana Press, 2001. http://dx.doi.org/10.1385/159259140x.

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Asch, Adam S., Maria J. Ruiz-Echevarria, Jared Whelan, Thomas Green, Biree Andemariam, Douglas Weidner und Nance Hamel. „Abstract 4234: Translational regulation mediates hematopoietic progenitor cell generation in embryonic stem cell culture“. In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-4234.

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The development of novel methods for the isolation of primary stem and progenitor cells is important for the treatment of blood cancers, tissue engineering, and basic research in the biomedical sciences. Our lab has previously shown that microtubes coated with P-selectin protein can be used to capture and enrich hematopoietic stem and progenitor cells from a mixture of cells perfused through the tube at physiologically-relevant shear stresses[1][2], and that using a surface coating of colloidal silica nanoparticles (12 nm diameter, 30% by weight SiO2) increased cell capture and decreased rolling velocity[3]. Here we show that 50 nm colloidal silica nanoparticle coatings may similarly increase cell capture, and that these protocols are effective for enrichment of human adult CD34-positive HSCs from primary apheresis and bone marrow aspirate samples. Future research may include long-term colony-forming assays to confirm stem cell activity of enriched cells, and transplantation in immune-deficient mice.

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Charles, Nichola, Jane L. Liesveld und Michael R. King. „Geometry Optimization of a Flow-Based Device to Maximize Selectin-Mediated Hematopoietic Stem Cell Enrichment“. In ASME 2008 6th International Conference on Nanochannels, Microchannels, and Minichannels. ASMEDC, 2008. http://dx.doi.org/10.1115/icnmm2008-62228.

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Rare cell enrichment techniques must selectively capture and successfully retain cells that exist at < 5% in a suspension. We developed a device to capture hematopoietic stem and progenitor cells (HSPCs) from adult bone marrow using immobilized adhesion molecules called selectins in the presence of a flow field. While we continue to optimize the immobilized protein surface and improve the selectivity of the device for HSPCs, it appears to be at the expense of cell recovery. To address this issue, we used experimental and computational methods to identify the hydrodynamic factors that contribute to cell capture, and present new designs for the device that could improve HSPC recovery without affecting the selectivity. We tested KG1a cell recovery using four configurations of tubing — straight cylindrical, helical, flattened and axially pinched, and two cell loading conditions: static and continuous oscillatory. We utilized COMSOL 3.4 finite element modeling software to investigate the path of particles introduced into these geometries, the fluid velocities and local wall shear stresses, and the predicted recovery efficiency based on the number of particles that contact and stick to the walls of the geometries. We found that, experimentally, the highest number of cells were recovered using static cell loading in a straight cylindrical tubing, but we predict that a corrugated or pinched geometry could further increase recovery under desirable flow conditions.

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Giles, Amber J., Meera Murgai, Yorleny Vicioso, Steven Highfill, Miki Kasai, Linda Vahdat, Leonard Wexler, Crystal Mackall, David Lyden und Rosandra Kaplan. „Abstract 4725: Hematopoietic stem cell niche activation and progenitor mobilization mediate cancer-associated immunosuppression and metastasis“. In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-4725.

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Wu, Mei X., und Jingke Yang. „LLL promotes engraftment of human umbilical cord blood-derived hematopoietic stem and progenitor cells“. In Mechanisms of Photobiomodulation Therapy XVI, herausgegeben von James D. Carroll, Praveen Arany und Ann Liebert. SPIE, 2021. http://dx.doi.org/10.1117/12.2583150.

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Lewis, Michael T. Unmasking Stem/Progenitor Cell Properties in Differentiated Epithelial Cells Using Short-term Transplantation. Fort Belvoir, VA: Defense Technical Information Center, August 2006. http://dx.doi.org/10.21236/ada462432.

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Lee, Adrian V. Novel Transgenic Mouse Model for Testing the Effect of Circulating IGF-I on Mammary Stem/Progenitor Cell Number and Tumorigenesis. Fort Belvoir, VA: Defense Technical Information Center, August 2008. http://dx.doi.org/10.21236/ada494145.

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Ji, Conghua, Rongchen Dai, Hanting Wu, Qiushuang Li, Shan Liu, Peijie He, Juan Liang und Qing Guo. Efficacy and safety of hematopoietic stem cell transplantation for hematologic malignancies: A protocol for an overview of systematic reviews and meta-analyses. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, Mai 2021. http://dx.doi.org/10.37766/inplasy2021.5.0064.

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Yin, Xuewei, Liming Yu, Lingling Yin, Yan Wang, Wei Zheng, Jie Xu, Yueli Liu et al. Efficacy and safety of tandem versus single autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma: A protocol for systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, Juni 2021. http://dx.doi.org/10.37766/inplasy2021.6.0112.

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