Дисертації з теми "Pancreatic differentiation"
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Yuan, Songyang. "Differentiation and transdifferentiation of adult pancreatic cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ30425.pdf.
Повний текст джерелаMyatt, Emily-Jane. "Differentiation of pancreatic and hepatic cell types." Thesis, University of Bath, 2013. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616573.
Повний текст джерелаDecker, Kimberly Jean. "Gata6 regulates pancreatic branching morphogenesis and endocrine differentiation /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Знайти повний текст джерелаTypescript. Includes bibliographical references (leaves 160-175). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
Kimura, Yoshito. "ARID1A Maintains Differentiation of Pancreatic Ductal Cells and Inhibits Development of Pancreatic Ductal Adenocarcinoma in Mice." Kyoto University, 2018. http://hdl.handle.net/2433/235986.
Повний текст джерелаBlyszczuk, Przemyslaw. "Differentiation of embryonic stem cells into pancreatic insulin-producing cells." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=97560032X.
Повний текст джерелаMurad, Nadia Yousif. "Differentiation of human embryonic stem cells to the pancreatic lineage." Thesis, University of Sheffield, 2008. http://etheses.whiterose.ac.uk/6102/.
Повний текст джерелаShah, Nadia Nisa. "Human embryonic stem cells : prospects for pancreatic β-cell differentiation". Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495052.
Повний текст джерелаUroić, Daniela Sonja. "Differentiation of embryonic stem cells towards pancreatic β-like cells". Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=167694.
Повний текст джерелаChong, Tsz-yat Ian, and 莊子逸. "Inducing the progressive differentiation of hESCs into pancreatic progenitor cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196433.
Повний текст джерелаpublished_or_final_version
Biochemistry
Master
Master of Philosophy
Gsour, Amna. "Differentiation of human cell line towards a pancreatic endocrine lineage." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/differentiation-of-human-cell-line-towards-a-pancreatic-endocrine-lineage(0c2c21fe-724d-449f-804c-02741c89828c).html.
Повний текст джерелаHalvorsen, Tanya L. "Growth regulation and differentiation in the human pancreatic beta cell /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p3000408.
Повний текст джерелаYeo, Wendy Wai Yeng. "Differentiation of skeletal muscle-derived stem cells into beta pancreatic lineage." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS091.
Повний текст джерелаType 1 Diabetes (T1D) is characterized by high and poorly controlled glucose levels due to the destruction of insulin-secreting pancreatic ß-cells. However, current ß-cell replacement therapies, involving pancreas and pancreatic islet transplantation are technically demanding and limited by donor availability. While embryonic stem cells and induced pluripotent stem cells are intensely investigated, neither can be used due to safety issues. Skeletal muscle-derived stem cells (MDSC) are an attractive alternative cell source as they have the potential to undergo multilineage differentiation into beating pacemaker-like cells and neuronal cells. Hence, it is hypothesised that they can differentiate into pancreatic lineages. This led to the goals of this study, which were (1) to investigate the potential of MDSC to differentiate into mature insulin expressing cells in vitro and (2) to reduce hyperglycemia in mouse model type 1 diabetes. In this study, MDSC were isolated from mouse via a serial pre-plating based on the adhesive characteristics of cultured cells, in which the cells of interest adhered to plates at a later time for in vitro differentiation, while the non-adherence undifferentiated MDSC were used for in vivo study. The MDSC were found to spontaneously differentiate into islet-like aggregates and expressed ß-cell markers in vitro, as determined by immunofluorescence and reverse transcription PCR analyses. This was further confirmed by immunoblotting analysis showing expression of proteins required for ß-cell function, such as Nkx6.1, MafA and Glut2. The differentiation of MDSC into islet-like clusters demonstrated glucose responsiveness in vitro. In streptozotocin-induced T1D mouse models, intraperitoneal injection of the undifferentiated MDSC did not restore the blood glucose levels of the diabetic mice to normoglycemia despite successful engraftment of MDSC into the pancreatic tissues. Taken together, these data show that MDSC may serve as an alternative source of stem cells for the treatment of diabetes
Wright, Elli Alexander. "The differentiation of human embryonic stem cells towards a pancreatic endoderm lineage." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509868.
Повний текст джерелаChen, Jim-Ray. "Hepatocytic differentiation of normal but not neoplastic cultured rat pancreatic duct cells." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28996.
Повний текст джерелаThe technique of in vivo implantation of cells to subcutaneous and intraperitoneal sites is used as it not only reveals the intrinsic potential of the implanted cells but also reflects the effects of the microenvironment on phenotypic expression.
The results of these studies indicate that when implanted in vivo normal propagable cultured cells derived from the duct epithelium of adult rat pancreas develop phenotypic features of a hepatocyte, and that the extent of this phenotypic expression is influenced by the microenvironment in which these cells are implanted. When localized subcutaneously, the cells displayed partial differentiation toward hepatocytes but retained some of their ductal phenotype. In contrast, when the same cells were implanted intraperitoneally, they expressed the full phenotypic properties of mature hepatocytes. Both spontaneously- and chemically-transformed pancreatic ductal cell lines did not display phenotypic differentiation along the hepatocytic lineage after in vivo implantation. It is concluded that (1) pancreatic ductal cells can be the progenitor cell for pancreatic hepatocytes; (2) Neoplastic transformation of these cell lines results in partial or total loss of hepatoctyic differentiation.
Shepherd, Jessica. "Malignant transformation and differentiation of adult rat pancreatic duct cells in vitro." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61214.
Повний текст джерелаWith the use of normal adult rat pancreatic ductular cell lines, this work shows that four representative pancreatic carcinogens all display dose-related genotoxicity to rat pancreatic ductular cells in vitro. Further, repeated exposure to sublethal doses induced anchorage-independent growth. Transformed cells, injected subcutaneously into isogeneic newborn rats, produced malignant tumors with ductular morphology. A novel achievement of this work was the production of ductular adenocarcinomas using streptozotocin, previously reported as only inducing islet cell tumors.
Delaspre, Fabien. "Stepwise differentiation of pancreatic acinar cells from mES cells by manipulating signalling pathway." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/38364.
Повний текст джерелаDespite known involvement of pancreatic acinar cells in exocrine pathologies (pancreatitis and pancreatic cancer), the lack of normal cell-based models has limited the study of the alterations that occur in the acinar differentiation program. We have previously shown that mESC (murine embryonic stem cells), which are pluripotent, can acquire an acinar phenotype in vitro. This was achieved, in part, by a combination of signals provided by the culture of foetal pancreases which was, however, no specific for the acinar lineage. The aim of this work was to develop a protocol selective for the acinar lineage based on the sequential activation of signaling pathways that recapitulate pancreatic development in vivo, through the definitive endoderm formation, the pancreatic and acinar specification and the expansion/differentiation of acinar progenitors. Treatment of embryoid bodies with Activin A enhanced the expression of endodermal genes as previously described. Subsequent treatment with Retinoic acid, FGF10 and Cyclopamine, an inhibitor of the Hedgehog pathway, resulted in the enhancement of pancreatic progenitor markers Pdx1, Ptf1a and Cpa1 but also of those expressed in the hepatic lineage, which were reduced by BMPs inhibition. Cells were further cultured in Matrigel using a 3D culture system in the presence of follistatin, dexamethasone, and KGF leading to a significant enhancement of the mRNA and protein levels of acinar markers while decreasing the expression of endocrine ones. Moreover, active Amyl was released into the medium. These data indicate that the selective activation of the acinar differentiation program in ES cells can be achieved by stepwise induction of signaling pathways involved in pancreatic exocrine development providing a potential tool for studying pancreatic differentiation and pancreas-related diseases.
Massumi, Mohammad. "Directed Differentiation of ES cells by pancreatic transcription factors p48, RBPJL and Mist1." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7231.
Повний текст джерелаDespite known involvement of acinar cells in pancreatic exocrine pathologies (i.e pancreatitis and pancreatic cancer), the lack of normal cell-based models has limited the study of the alterations that occur in the acinar differentiation program. Our previous data showed that mES (murine embryonic stem) cells, which are pluripotent and have the ability to generate specialized cell types, can acquire an acinar phenotype in vitro. The aim of this work was to increase the digestive enzyme content of the generated cells as well as their functional properties based on stable overexpression of p48, RBPJL and Mist1 by lentiviral gene transduction. Thus, we engineered transgenic mES cell lines constitutively expressing RBPJL and/or Mist1 using a multi-step infection strategy. The superimposition of p48 expression by lentiviral infection of differentiating cells resulted in a strong expression of digestive enzymes, with a pattern of regulation similar to what occurs in vivo during pancreatic development. In this induction, both p48 and RPBJL are indispensable. On the other hand, we showed a high increase in the production of several components of the secretory machinery which was dependent of Mist1. Importantly, p48/RBPJL/Mist1 cells exhibited a regulated-secretory in response to acinar secretagogues and a better secretion activity than the 266-6 acinar cell line. Combined expression of key genes involved in pancreatic development in ES cells may be a promising approach to better understand subtle steps of pancreatic exocrine development.
Lehnert, Lasse. "Morphological and molecular characterization of human pancreatic adenocarcinoma cells undergoing duct-like differentiation." [S.l.] : [s.n.], 2000. http://e-diss.uni-kiel.de/diss/d385.pdf.
Повний текст джерелаSvensson, Per. "Functional analysis of Ipf1/Pdx1, MFng and Id during pancreatic growth and differentiation." Doctoral thesis, Umeå universitet, Umeå centrum för molekylär medicin (UCMM), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1671.
Повний текст джерелаWang, Nan. "In vitro differentiation of mouse embryonic stem cells into pancreatic insulin-producing cells." Thesis, University of Nottingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508245.
Повний текст джерелаWeng, Chen. "SINGLE-CELL TRANSCRIPTOMICS OF HUMAN PANCREATIC ISLETS IN DIABETES AND ΒETA CELL DIFFERENTIATION". Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1612882103714773.
Повний текст джерелаKondo, Yasushi. "Identification of a small molecule that facilitates the differentiation of human iPSCs/ESCs and mouse embryonic pancreatic explants into pancreatic endocrine cells." Kyoto University, 2018. http://hdl.handle.net/2433/230976.
Повний текст джерелаCho, Hsin-Hua. "Differentiation of human embryonic stem cells into pancreatic progenitors using chemically defined culture systems." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608076.
Повний текст джерелаZhao, Min. "Molecular studies on the differentiation and proliferation of human pancreatic beta cells and exocrine cells." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405642.
Повний текст джерелаPiccand, Julie. "Regulation of pancreatic and intestinal endocrine cell differentiation and function : roles of Pak3 and Rfx6." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ057/document.
Повний текст джерелаPancreatic and intestinal endocrine cells, and their secreted hormones, contribute to the regulation of energy homeostasis. Their differentiation relies on similar genetic programs controlled by the proendocrine transcription factor Ngn3. However, our knowledge of the endocrinogenic programs implemented by Ngn3 is still fragmentary. Therefore, the transcriptome of endocrine progenitors has been determined in the lab. Among the genes which showed a strong enrichment in the endocrine lineage, I studied the expression and function of Pak3, a serine/threonine kinase and further pursued the dissection of the function of the transcription factor Rfx6 in the pancreas and the intestine. I showed that Pak3 is expressed throughout pancreas development and maintained in adult islets. Using ex vivo loss of function experiments and in vivo characterisation of the Pak3-deficient mice, I identified Pak3 as an inhibitor of islet progenitors and beta-cell proliferation in the embryonic mouse pancreas. Furthermore, we performed metabolic studies which revealed that Pak3-deficient micehave an impaired glucose homeostasis, especially under challenging high fat diet. In parallel, using a conditional knockout mouse for Rfx6, we showed that Rfx6 is necessary downstream of Ngn3 for endocrine cell differentiation in the pancreas as well as in the intestine. Finally, additional experiments in adult mice suggest that Rfx6 is necessary to maintain pancreatic beta-cells, enteroendocrine cell turnover and intestinal lipid absorption. In conclusion, these studies revealed two novel key players in the regulation of endocrine cell differentiation and energy homeostasis in the pancreas and the intestine
Santos, Cravo Ana Maria. "The role of epithelial cell de-differentiation in the context of improved chemotherapy applied to pancreatic cancer." Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.642055.
Повний текст джерелаJung, Matthias Verfasser], Gerald [Akademischer Betreuer] Moritz, Bernd [Akademischer Betreuer] [Fischer, and Heike [Akademischer Betreuer] Walles. "The establishment of non‐viral reprogramming methods and pancreatic differentiation in organotypic models for the production of patient‐specific pancreatic cells / Matthias Jung. Betreuer: Gerald Moritz ; Bernd Fischer ; Heike Walles." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2014. http://d-nb.info/1068504536/34.
Повний текст джерелаDaoud, Jamal. "Development of a three-dimensional microenvironment and dielectric monitoring system for long-term «in vitro» culture and differentiation of human pancreatic islets." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104749.
Повний текст джерелаLa transplantation humaine d'îlots pancréatiques se présente comme une méthode intéressante pour le traitement du diabète de type I au niveau cellulaire. Cependant, plusieurs problèmes persistants limitent l'efficacité de la procédure de transplantation; les principaux sont le manque de tissu pancréatique disponible et la viabilité des îlots après leur isolement. Ces obstacles sont surmontés par des méthodes de préservation, de culture, et d'expansion in vitro à long terme d'îlots isolés afin de parvenir à des populations d'îlots fonctionnellement viables pour des fins de transplantation. Cette thèse présente un nouveau système qui favorise la préservation et la culture in vitro d'îlots pancréatiques humains dans un microenvironnement contrôlé et surveillé de manière non invasive. Le développement de ce système est réalisé en quatre étapes successives : i) l'optimisation d'un substrat 2D de matrice extracellulaire modifié en surface, ii) la fabrication d'un échafaudage interconnecté à géométrie contrôlée, élément approprié à la culture des îlots, iii) la culture in vitro 3D intégrant le substrat de la matrice optimisé et l'échafaudage fabriqué, et iv) l'intégration des microenvironnements en trois dimensions au sein d'un bioréacteur à perfusion multi-sources, couplé avec des électrodes de mesure diélectrique pour la culture in vitro à long terme des îlots pancréatiques humains. Plusieurs nouveautés attribuées au système développé sont également présentées. Les études 2D révèlent que la fibronectine améliore la fonctionnalité et la morphologie de l'insuline dépendant du glucose, tandis que les collagènes I/IV contribuent à l'adhésion. Les échafaudages en PLGA (acide poly-lactique-co-glycolique) micro-fabriqués ont été élaborés de façon à fournir des structures poreuses et une inter-connectivité complète de manière reproductible et géométriquement contrôlée. De plus, l'incorporation de composants optimisés de matrices extracellulaires dans les échafaudages a été accomplie grâce à un enrobage des îlots dans un gel de matrices extracellulaires semé dans les structures poreuses d'échafaudages micro-fabriqués. Le microenvironnement 3D a favorisé la culture à long terme d'îlots humains, donnant des indices élevés de libération d'insuline d'approximativement 1.8, tout en augmentant l'expression des gènes des îlots. Enfin, un bioréacteur à perfusion multi-sources, équipé d'un système de surveillance d'impédance électrique par spectroscopie diélectrique, est utilisé pour la culture 3D contrôlée des îlots isolés. Ce système permet de surveiller à long terme la différenciation et la re-différenciation des îlots pancréatiques humains dans un microenvironnement 3D contrôlé, donnant une population dont les caractéristiques morphologiques et fonctionnelles en particulier équivalent à celles d'îlots fraîchement isolés.
Kuen, Janina [Verfasser], Manfred [Gutachter] Lutz, and Alois [Gutachter] Palmetshofer. "Influence of 3D tumor cell/fibroblast co-culture on monocyte differentiation and tumor progression in pancreatic cancer / Janina Kuen ; Gutachter: Manfred Lutz, Alois Palmetshofer." Würzburg : Universität Würzburg, 2017. http://d-nb.info/1149510390/34.
Повний текст джерелаMcBain, Stuart C. "Development of an inducible expression system to regulate protein expression in pancreatic beta cells : studies of IRS-2 and wolframin in relation to beta cell growth and differentiation." Thesis, Keele University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288431.
Повний текст джерелаVaissié, Alix. "Alternatives to “native human islets” for research in vitro and in vivo : pseudo-islets and pancreatic endocrine cells from pluripotent stem cells – the role of progerin in differentiation and maturation." Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S035.
Повний текст джерелаIntroduction: The use of human islets of Langerhans is the gold standard for research, both for physiological research and for the development of new therapeutic molecules for the treatment of type 2 diabetes. The demand of human islets for research projects is constantly growing however, the availability is limited and different islet preparations show significant variability between human pancreata.Objectives: The main objective of this thesis was to propose an alternative to native human islets that can provide homogeneous and abundant pancreatic islets for research. To do this, we had two main objectives: 1) the production of controlled diameter pseudo-islets from human pancreata, and the evaluation of their function in vitro and in vivo compared to their native islet counterparts; 2) the optimization of the production of pancreatic endocrine cells from different pluripotent stem cell lines and evaluation of the impact of progerin on the differentiation and maturation of the cells produced. Pluripotent stem cells from healthy donors (H1, WiCell) and from patients affected with accelerated aging disease Progeria (HGPS, iStem).Material and Methods: The pseudo-islets were formed in clinical islet medium (CMRL 1066 human albumin, insulin) 7 days using the 5D Sphericalplate (Kulgelmeiers) and compared to the native islets D1 (day 1) and D7 (day 7) from the same donor.The differentiation of pluripotent stem cells (iPS DF19.9, H1 and iPS HGPS cells) was optimized using different protocols: the Rezania protocol, the SD Kit (StemCell Technologies) and the Nostro protocol. For in vitro maturation gene expression among different cell lines was evaluated by qPCR. Protein expression was assessed by immunofluorescence technique and Flow cytometry analysis (EGID).For in vivo maturation, after transplantation under the kidney capsule of immunodeficient mice, blood glucose and human c-peptide measurements were assessed as well as metabolic test such as IPGTT were performed.Results: The pseudo-islets (n=4) generated in clinical islet medium secreted significantly less insulin in vitro than the native islets at D1 but with no significant difference from the native islets at D7. In both groups at D7, a significant decrease in intracellular insulin was observed compared10to native islets at D1. In vivo, the native islets at D1 secrete significantly more human c-peptide than the native islets at D7, while the difference is not significant between the native islets at D1 and the pseudo-islets at D7. In addition, morphometric analysis of the grafts revealed that the pseudo-islets tend to have more glucagon positive cells than the other two groups.Optimization of the differentiation of pluripotent stem cells allowed us to obtain more than 95% endoderm for H1 cells and 80% for iPS HGPS cells. For both lines, we generated 95% of pancreatic progenitor cells. The comparison of maturation genes revealed that progerin lead to a slight increase of cell maturation in the iPS HGPS group compared to H1 cells. However, no differences in in vivo function was observed. Age-related markers (53BP1, IGF1r, p16 and yH2AX) which validated in a pancreas from an elderly donor and an insulinoma. We identified yH2AX after 6 months transplantation of H1-grafts in endocrine and non-endocrine cells, while the expression in iPS HGPS-grafts appeared in the majority of cells, which had various shape of nucleiConclusion: This work provided positive results in terms of functional pseudo-islets and stem cells derived pancreatic endocrine cells. However, they remain preliminary and further studies must be conducted to provide realistic alternatives to native human islets for research
Rovira, Clusellas Meritxell. "Estrategias para la diferenciación in vitro de células ES de ratón a células acinares pancreáticas." Doctoral thesis, Universitat Pompeu Fabra, 2007. http://hdl.handle.net/10803/7104.
Повний текст джерелаLas células madre embrionarias (ES) de ratón han sido utilizadas en la última década para generar in vitro células completamente diferenciadas de varios linajes celulares. No obstante, la capacidad de las células ES a diferenciarse a tipos celulares de origen endodérmico es muy limitada. El objetivo principal de este proyecto ha consistido en desarrollar estrategias para diferenciar células ES de ratón a células pancreáticas acinares con una elevada eficiencia mediante 1) la optimización de las condiciones de cultivo con tal de activar vías de señalización implicadas en el desarrollo/diferenciación pancreáticas; 2) la sobreexpresión de factores transcripcionales maestros utilizando vectores virales con el fin de recapitular específicamente un programa de diferenciación acinar; 3) la selección genética de las células comprometidas al linaje acinar con el objetivo de purificar las células acinares diferenciadas.
Mediante la integración de estos abordajes, hemos conseguido aislar células que comparten características fenotípicas con células acinares inmaduras según la expresión de marcadores de diferenciación y la respuesta funcional a secretagogos.
Exocrine pancreatic diseases such as chronic pancreatitis (PC) or pancreatic cancer are major health issues in Europe. In CP, the acinar tissue is substituted by ductal complexes. In addition, it is difficult to maintain the differentiated phenotype of the acinar cells in culture as within few days an acinar-ductal transdifferentiation takes place.
In the last decade, mouse embryonic stem cells (mES) have been used to generate differentiated cells of a variety of cellular lineages in vitro. However, the ability of ES cells to differentiate into endodermal lineages is limited. The main objective of this project has focused on the development of strategies to differentiate mES to pancreatic acinar cells with high efficiency by means of: 1) Optimization of cell culture conditions to activate signalling pathways involved in pancreatic differentiation/development; 2) the overexpression of master transcription factors involved in pancreas development using viral vectors in order to recapitulate specific acinar differentiation program; 3) the genetic selection of cells committed to the acinar linage in order to purify the differentiated cells.
The integration of these different strategies allowed us to isolate cells that share phenotypic features with immature acinar cells according to the expression of differentiation markers and the functional response to acinar secretegogues.
Campos, Maria Luisa Morais Sarmento de. "ICAT: a novel Ptf 1A/P48 partner that modulates acinar expression." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7233.
Повний текст джерелаPtf1a/p48 es un factor de transcripción bHLH específico del páncreas necesario durante los estadios tempranos del desarrollo embrionario para la formación del mismo, y para el correcto funcionamiento del páncreas exocrino en el adulto. P48 desempeña también una función antiproliferativa, la cual puede resultar en una actividad de supresión tumoral. En el presente estudio, basado en una estrategia de cribado de doble-híbrido en levadura, han sido identificadas nuevas proteínas que interaccionan y que modulan la actividad específica de p48. Entre las posibles proteínas que interaccionan y han sido identificadas de novo se encuentra p/CAF, un co-activador que potencia la actividad transcripcional de p48, y ICAT, un inhibidor de la vía de señalización de la β-catenina. Se ha demostrado que ICAT se une a p48 y ambos son co-expresados en el páncreas durante el desarrollo y en el adulto. Utilizando diferentes modelos celulares, la sobreexpresión de ICAT en células tumorales acinares resultó en un cambio en el patrón de expresión de genes específicos del páncreas. Al mismo tiempo, se observó que niveles elevados de ICAT inhiben la interacción entre p48 y su co-activador p/CAF. Mientras que este complejo hetero-oligomérico es necesario para la expresión de los genes acinares, se demostró que ICAT está presente en un complejo PTF1 reconstituido in vivo. Finalmente, se observaron alteraciones en la expresión de ICAT en varios tipos histológicos de tumores pancreáticos, que posiblemente contribuyen a su fenotipo de diferenciación y propiedades neoplásicas.
Schroeder, Insa S., Sabine Sulzbacher, Tobias Nolden, Jörg Fuchs, Judith Czarnota, Ronny Meisterfeld, Heinz Himmelbauer, and Anna M. Wobus. "Induction and Selection of Sox17-Expressing Endoderm Cells Generated from Murine Embryonic Stem Cells." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135990.
Повний текст джерелаDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
Schroeder, Insa S., Sabine Sulzbacher, Tobias Nolden, Jörg Fuchs, Judith Czarnota, Ronny Meisterfeld, Heinz Himmelbauer, and Anna M. Wobus. "Induction and Selection of Sox17-Expressing Endoderm Cells Generated from Murine Embryonic Stem Cells." Karger, 2012. https://tud.qucosa.de/id/qucosa%3A27696.
Повний текст джерелаDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
Augustine, Tanya Nadine. "The differentiation of hepatic stem cells into pancreatic endocrine tissue: the influence of pancreatic mesoderm." Thesis, 2008. http://hdl.handle.net/10539/5858.
Повний текст джерелаLu, Chung-Kuang, and 盧重光. "Investigating Transcriptional And Post-transcriptional Regulation in Pancreatic Cell Differentiation." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/ny6bpg.
Повний текст джерела國立中正大學
分子生物研究所
102
During pancreas development, many transcription factors function coordinately to ensure normal differentiation of different cell types. In particular, Pdx1, Ptf1a, and Neurog3 play pivotal roles in the growth and lineage specification of pancreatic multipotent progenitor cells (MPCs). Ptf1a is essential for both exocrine pancreas development and maintenance of acinar cell differentiation. The bHLH transcription factor Neurog3 controls pancreatic endocrine cell fate specification in MPCs. However, additional factors which modulate the genetic network to complete the developmental process are much less noticed. Here, I investigate the roles of several novel factors that could be involved in the regulation of pancreatic cell differentiation. Based on a previous differential screening assay, Rbms3 (RNA binding motif, single strand interacting protein 3) was identified. RBMS3 contains two RNA-binding motif and bind tightly to A/U oligoribonucleotides, suggesting that it is an RNA-binding protein. I found that RBMS3 was specifically expressed in the pancreatic rudiment. Next, I showed that RBMS3 specifically bound to the 3’UTR of Ptf1a mRNA, but not the 3’UTR of Pdx-1. Ectopic expression of RBMS3 increased the expression of a reporter gene carrying the Ptf1a 3’UTR. Down-regulation of Rbms3 in the AR42J-B13 pancreatic exocrine cell line affected the expression of endogenous PTF1A protein and its downstream target genes. These results revealed a novel mechanism of post-transcriptional regulation in controlling exocrine pancreas development. On the other hand, two other factors that I investigated, Ccar1 (Cell cycle and apoptosis regulator 1) and Zfp668 (Zinc finger protein 668), appeared to be involved in regulating endocrine differentiation at the transcriptional level. These two factors were previously identified from a yeast two-hybrid screening for interacting with NEUROG3 in our laboratory. The interactions between NEUROG3 and CCAR1, ZFP668 have been further verified using GST pull-down assay and Co-IP experiment. CCAR1 protein has been shown to play the role as a co-activator of nuclear receptors (NRs) to recruit mediator complex. Interestingly, from luciferase reporter gene assays, we found that CCAR1 was required for NEUROG3 to activate the expression of the reporter genes containing Neurod1 promoter. Furthermore, when endogenous levels of Ccar1 were reduced by a shRNA transduction in the PANC-1 pancreatic ductal cell line, NEUROG3-induced the expression of its target genes and the transdifferentiation program were compromised. These results suggest that CCAR1 is one of the competence factors that enable pancreatic progenitor cells to respond to the induction by NEUROG3 and differentiate into endocrine cells. ZFP668 belongs to the krüppel C2H2-type zinc finger protein family and contains 16 C2H2-type zinc fingers, indicating its role as a DNA-binding protein. So far, the function of Zfp668 has remained entirely unexplored. To understand the role of ZNF668 in pancreatic endocrine cell differentiation, I performed an immunohistochemical staining of ZFP668 expression and found that ZFP668 is abundantly expressed in mouse embryonic pancreas. I next demonstrated that ZFP668 was a nuclear protein that physically interacted with NEUROG3 and CCAR1, respectively. I also verified that ZFP668 could cooperate with NEUROG3 in activating Neurod1 and Insm1 expression by using luciferase reporter gene assays. Likewise, down-regulation of endogenous Zfp668 in the PANC-1 cell inhibits the transdifferentiation program initiated by NEUROG3. On the other hand, ZFP668 does not affect the stability of NEUROG3 protein. The results described above may elucidate the transcriptional regulation of NEUROG3-mediated pancreatic endocrine cell differentiation.
Thatava, Tayaramma. "Differentiation of bone marrow stem cells into functional pancreatic insulin-producing cells /." 2007. http://www.gbv.de/dms/bs/toc/526576839.pdf.
Повний текст джерела"Isolation, characterization and differentiation of pancreatic progenitor cells from human fetal pancreas." Thesis, 2007. http://library.cuhk.edu.hk/record=b6074338.
Повний текст джерелаDue to the scarcity of fetal pancreas for generating functional insulin-secreting cell clusters for sufficient islet transplantation, we targeted for searching pancreatic stem/progenitor cells. Putative PSCs can be aggregated and differentiated into islet-like cell clusters (ICCs) when exposed to serum-free medium containing various conventional growth factors, including HGF, GLP-1, betacellulin and nicotinamide.
Fetal pancreatic tissue consisting of immature progenitor cells serves as a potential source of stem cells as they possess a higher replicative capacity and longevity than their adult counterparts.
Two novel candidates and a key pancreatic transcription factor on the PSC/ICC proliferation and differentiation were investigated in the present study. One of them is a ubiquitously expressed multi-PDZ-domain protein, PDZ-domain-containing 2 (PDZD2), which was previously found to express in the mouse beta cells and exhibit mitogenic effects in beta cell line. Results showed that PDZD2 was detected in high levels in both human fetal pancreas and in PSCs. Results indicate the potential involvement of PDZD2 in regulating PSCs proliferation and differentiation and pancreatic development.
Suen Po Man, Ada.
"July 2007."
Adviser: P.S. Leung.
Source: Dissertation Abstracts International, Volume: 69-01, Section: B, page: 0051.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2007.
Includes bibliographical references (p. 194-214).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts in English and Chinese.
School code: 1307.
Chan, Shun-Hung, and 詹蕣璜. "Functions of HIF2 alpha and NeuroD in Zebrafish Pancreatic Beta-Cell Differentiation." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/k7tsdx.
Повний текст джерела國立臺灣海洋大學
生物科技研究所
102
NeuroD is a basic helix-loop-helix (bHLH) transcription factor that plays important roles in vertebrate CNS, retina and pancreas development. Overexpression of neurod in in Xenopus embryos induces early neuronal differentiation. Patients with Neurod mutation suffer MODY6 diabete syndrome due to dysfunctional pancreas. The pancreas β cell development is mediated by NeuroD. Previous studies demonstrated that HIF2α plays critical functions in CNS development. Depletion of HIF2α inhibited neurod expression and aboragged neuronal differentiation due to loss of birc5a expression. It is unclear whether neurod expression in pancreas β cell is also mediated by HIF2α. Here I demonstrated that the neurod expression in pancreatic cells is not mediated by HIF2α. Depletion of HIF2α did not prevent neurod transcription in pancreas cells. Furthermore, hif2α knockdown did not inbite insulin transcription in pancreas β cell. Conversely, most of neurod transcription in CNS regions was inhibited in hif2α morphants. In conclusion, this study demonstrated the neurod gene is regulated by different mechanism in neural cells and pancreas β cell.
Blyszczuk, Przemyslaw [Verfasser]. "Differentiation of embryonic stem cells into pancreatic insulin-producing cells / von Przemyslaw Blyszczuk." 2004. http://d-nb.info/97560032X/34.
Повний текст джерелаLiou, Shian-Wen, and 劉獻文. "Investigating a novel factor that collaborates with Ngn3 in mediating pancreatic endocrine differentiation." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/30964606548893289929.
Повний текст джерела國立中正大學
分子生物研究所
99
Previous studies have shown that several transcription factors are critical regulators of pancreatic development, such as PDX1, Ptf1a and Ngn3. In above mentioned, Ngn3 is especially important as a bHLH transcription factors that involved in development of all endocrine cell lineages and has been designated as a marker of islet precursor cells. To identify proteins which interact with Ngn3 and possibly modulate the activity of Ngn3 down-stream gene to regulate endocrine cell differentiation during pancreatic development. Previously, our laboratory has used yeast two-hybrid system to screen a mouse embryonic (E10.5) pancreatic bud cDNA library using Ngn3 as a bait. After an intensive screening, Zinc finger protein 668 (Zfp668), which contain 16 C2H2 type zinc finger motif, had been identified to interact with Ngn3. In my study, I have verified that Ngn3 has a direct binding with Zfp668 through GST pull-down assay, and subsequently used co-immunoprecipitation to prove the Ngn3-Zfp668 interaction in mammalian cells. To further dissect Zfp668 for motifs responsible for interacting with Ngn3, a series of GST-tagged Zfp668 truncate protein were purified. I found that the 80~164 and 278~542 amino acid region of Zfp668 are the shortest fraction to mediate the interaction with Ngn3. Significantly, I have also validated that Zfp668 could affect the expression of Ngn3 down-stream target (NeuroD) by luciferase reporter assay. Ectopic expression of Ngn3 and Zfp668 in PANC-1(human pancreatic carcinoma) cells with lentivirus also lead to the same conclusion. In addition, the stable PANC-1 cell line with Ngn3 or Zfp668 overexpression clone were established to determine the biological function of Zfp668.
Churchill, Angela Josephine. "Spatiotemporal and Mechanistic Analysis of Nkx2.2 Function in the Pancreatic Islet." Thesis, 2016. https://doi.org/10.7916/D84M94N2.
Повний текст джерелаThatava, Tayaramma [Verfasser]. "Differentiation of bone marrow stem cells into functional pancreatic insulin-producing cells / von Tayaramma Thatava." 2007. http://d-nb.info/983842833/34.
Повний текст джерела(11134677), Shiqi Tang. "Differentiation of Cav1.2 and Cav1.3 pharmacology and role of RyR2 in pancreatic beta-cell electrophysiology." Thesis, 2021.
Знайти повний текст джерелаThe L-type VGCC subtypes, including subtypes Cav1.1-1.4, have been shown to play critical roles in various cellular activities, including muscle contraction, hormone secretion, and neurotransmitter release. Recent research indicates the potential involvement of Cav1.3 in various neurological and psychiatric disorders, such as the early onset of Parkinson’s disease and substance abuse disorders. Non-selective L-VGCC subtype blockers such as dihydropyridines (DHPs) are used to treat hypertension and angina because they potently inhibit Cav1.2, but no selective Cav1.3 inhibitors have been developed yet. We resolved the molecular determinants to differentiate Cav1.2 and Cav1.3 in response to DHP nifedipine. Nifedipine IC50 for Cav1.2 and Cav1.3 are 22nM and 289nM determined by whole-cell patch-clamp. We identified two significant amino acids, Cav1.3/M1030 to Cav1.2/V1036 in the transmembrane IIIS5 and Cav1.3/S1100 Cav1.2/A1106 in the extracellular IIIS-3P loop, to differentiate the subtype affinity to nifedipine.
We found that the Cav1.3/II-III loop fused to eGFP decreased glucose-activated action potential (GSAP) frequency by ~80% in the pancreatic β-cell. We introduced several synthetic peptides, and peptide P3-1 from C-terminal induced a -16mV shift in V1/2 inactivation with an EC50 of 231nM. P3-1 contains a protein kinase G (PKG) phosphorylation site (RRISE) required for PKG inhibition of Cav1.3 current but not conserved in Cav1.2. We found that the shift in V1/2 inactivation induced by co-expression of Cav1.3 with the Cav1.3/II-III loop/GFP requires the presence of a Cavβ subunit, and Cavβ3 also exhibits selectivity over other β subunits. Significantly, P3-1 shifts the Cav1.2 inactivation to a more positive voltage when co-expressed with either Cavβ2a or Cavβ3, demonstrating the ability of P3-1 to differentiate Cav1.2 and Cav1.3 in a Cavβ-dependent manner.
Failure of pancreatic β-cells to secrete enough insulin to maintain glucose homeostasis is a hallmark of Type 2 diabetes. However, the consequences of the dysregulation of the endoplasmic reticulum (ER) Ca2+ channel ryanodine receptor-2 (RyR2) in pancreatic β-cells are not fully understood. Therefore, we characterized the electrical activity in INS-1 in which RyR2 has been deleted via CRISPR/Cas9 gene editing. We observed a decreased level of IP3 receptor binding protein (IRBIT) in RyR2KO INS-1 cells and generated IRBITKO INS-1 cells. VGCC current density in RyR2KO doubled compared to controls and was also elevated in IRBITKO compared to control cells. All HVA Ca2+ channels were upregulated, determined by fractional current blocked by nifedipine. We also found that GSAP frequency is doubled by RyR2 deletion due to failure to activate apamin sensitive SK (small conductance calcium-activated potassium) channels.
Wang, Sui. "The Myt1 and Ngn3 feed-forward expression loop drives pancreatic islet differentiation in the mouse." Diss., 2009. http://etd.library.vanderbilt.edu/available/etd-11262009-124114/.
Повний текст джерелаKuen, Janina. "Influence of 3D tumor cell/fibroblast co-culture on monocyte differentiation and tumor progression in pancreatic cancer." Doctoral thesis, 2017. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-156226.
Повний текст джерелаBei Bauchspeicheldrüsenkrebs handelt es sich um eine maligne Tumorerkrankung, deren Behandlung Ärzte noch immer vor große Herausforderungen stellen und die zur dritthäufigsten krebsbedingten Todesursache der westlichen Welt zählt. Desmoplastische Reaktionen im Tumorgewebe sind hierbei ein besonderes Merkmal dieser Erkrankung. Dabei spielen tumor-assoziierte Fibroblasten sowie unterschiedliche Zellen des Immunsystems und deren Interaktionen eine essentielle Rolle hinsichtlich Tumorwachstum und der Herunterregulation des Immunsystems. Um zelluläre Mechanismen, die ein immunsuppressives Tumormilieu induzieren, zu identifizieren, entwickelten wir ein 3D Ko-Kultur Modell mit Bauchspeicheldrüsenkrebszellen, tumor-assoziierten Fibroblasten sowie Monozyten und T-Zellen. Mit Hilfe dieses Modells konnten wir den Einfluss von Tumorzellen und Fibroblasten auf den Phänotyp und das Verhalten von Monozyten untersuchen. Dazu wurden Monozyten in einer 3D Tumorzell/Fibroblasten Ko-Kultur kultiviert und differenziert, um anschließend die Expression definierter Zelloberflächenmarker und löslicher Faktoren zu analysieren. Des Weiteren wurde das Verhalten dieser 3D Ko-Kultur differenzierten myeloiden Zellpopulation sowie ihre Fähigkeit den Phänotyp von T Zellen und deren Proliferation zu beeinflussen untersucht. Die 3D Ko-Kultur der Monozyten zusammen mit den Tumorzellen und den Fibroblasten führten zur Produktion immunsuppressiver Zytokine und Chemokine, wodurch die Differenzierung der Monozyten in M2-ähnliche Makrophagen induziert wurde. Diese durch die 3D Tumorzell/Fibroblasten Sphäroide polarisierten aus Monozyten herangereiften M2-ähnlichen Makrophagen besaßen außerdem immunsuppressive funktionelle Eigenschaften, indem sie in der Lage waren, die Aktivierung und Proliferation von autologen CD4+ und CD8+ T Zellen in vitro zu inhibieren. Die Suppression sowohl der CD4+ als auch der CD8+ T Zellen konnte durch die Behandlung therapeutischer Moleküle, die die Re-Aktivierung der immunsuppressiven 3D Sphäroid polarisierten Makrophagen stimulierten oder suppressive Faktoren wie Arginase-I blockierten, wieder aufgehoben und die T Zell Proliferation teilweise wiederhergestellt werden. Unser etabliertes 3D Ko-Kultur System repräsentiert ein vielversprechendes physiologisch relevantes Modell, welches genutzt werden kann, um Zell-Zell Interaktion und Kommunikation im Tumormilieu zu untersuchen und dadurch die Wirkung von Medikamenten zu verbessern. Ein gezieltes besseres Verständnis von Tumorresistenz Mechanismen gegen bereits bestehende Immun Therapien fördert die Entwicklung neuer therapeutischer Ansätze zur Bekämpfung von Krebs
Yi-Hsien, Fang, and 方議賢. "Investigating the influence of ZFP668 on pancreatic endocrine cell differentiation using ex vivo tissue culture system." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/55928346031382170753.
Повний текст джерела國立中正大學
生物醫學研究所
104
The pancreas is a glandular organ in the digestive system and endocrine system of vertebrates. It controls blood glocuse stability. Transcription factors such as PDX1、Ptf1a(P48) and Ngn3 function coordinately to regulate pancreas development during embryonic development.. Neurogenin3 (Ngn3) is a member of the basic helix-loop-helix family. It controls the development and formation of the endocrine cells ‚such as α cells、β cells、ε cells、δ cells、PP cells. Previous study has shown that Zinc finger protein 668 (ZFP668),which contains 16 C2H2 type zinc finger motif can interact with Ngn3. ZFP668 has been identified to interact with Ngn3 by GST-pull down assay and co-immunoprecipitation (Co-IP) experiment. Our previous study has also shown that ZFP668 could regulate the expression of Ngn3’s downstream target genes such as NeuroD1 and Insm1. The aim of my project, is to clarify whether ZFP668 could modulate endocrine cells differentiation. I used β cell line- NIT1 and ex vivo embryonic pancreas bud culture as my experimental model. First‚ I suppress the ZFP668 expression by lentivirus infection in both model. After ZFP668 is knocked down, I analysed the Ngn3 downstream genes expression in NIT1 cells. On the other hand‚ I also dissected the embryonic pancreas bud from mouse embryos, infected with lentivirus and then cultured the cells for seven days. Finally, I used immunostain to detect the lentivirus infected cells which co-expressed endocrine cell markers. Then, I investigated whether knockdown ZFP668 can affect endocrine cells differentiation. In order to further confirm whether ZFP668 can affect endocrine cell differentiation, I established the ES cells differentiation model. I induced ES cells to differentiate into insulin-producing cells and analysed the expression of pancreatic endocrine markers during differentiation. The current results show that endoderm markers can be detected, and some endocrine cell markers can also be deceted during ES cell differentiation process. These results confirmed that ES cell can be induced to differentiate into pancreas like cell. However, different conditions for the induction, including culture medium and different combination of growth factors for treating ES cell, need to be explored to improve the efficiency of pancreatic cell differentiation at final stage.
Wu, Yi-Chuan, and 吳宜娟. "Effects of Lotus Leaf Methanolic Extract on Pancreatic Lipase Activity and Differentiation of 3T3-L1 Preadipocytes." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/36430238472993842798.
Повний текст джерела臺灣大學
食品科技研究所
95
Obesity is the most common nutritional disorder and it is considered to be a risk factor associated with the development of the major human diseases, including cardiovascular disease, diabetes, and cancer. It is an important topic in the world of public health and preventive medicine. It has close relations with lipid absorption and pancreatic lipase activity. The differentiation of 3T3-L1 preadipocytes plays an important role on the mechanism of adipogenesis. In the research about lotus (Nelumbo nucifera Gaertn.) leaf methanolic extract (LLM) on pancreatic lipase activity and differentiation of 3T3-L1 preadipocytes is rare. The aim of the present study was to assess the effects of LLM on pancreatic lipases activity and differentiation of 3T3-L1 preadipocytes. LLM were screened for inhibitory effects on pancreatic lipase (PL) activities as well as on triglyceride (TG) accumulation in 3T3-L1 preadipocytes to find the effective fractions, subfractions and active compounds that having the anti-obesity trend. Six flavonoids were separated from LLM, including quercetin, quercetin-3-O-glucoside, quercetin-3-O-glucuronide, quercetin-3-O-galactoside, catechin and kaempferol-3-O-glucoside. In pancreatic lipase activity-inhibiting assay, quercetin exhibited significant inhibitory effects at the concentration of 50 μM with 75% pancreatic lipase activity v.s control (p<0.05). In 3T3-L1 preadipocyte experiment, subfractions 1, 3 and 4 of LLME (LLM ethyl acetate partition) markly inhibited about v 25% of lipid accumulation in 3T3-L1 cells at the concentration of 50 μg/mL. Moreover, quercetin and quercetin-3-O-galactoside were found to inhibit TG accumulation in 3T3-L1 cells at the concentration of 50 μΜ with 15% and 18%. Subfraction 3 of LLME could reduce expression of PPARγ and C/EBPα mRNA, especially mRNA expression-inhibiting of C/EBPα is more apparent than PPARγ. Consequently, LLM could reduce pancreatic lipase activity, inhibit the differentiation of 3T3-L1 preadipocytes and decrease TG accumulation in 3T3-L1 cells.
Lehnert, Lasse [Verfasser]. "Morphological and molecular characterization of human pancreatic adenocarcinoma cells undergoing duct-like differentiation / vorgelegt von Lasse Lehnert." 2000. http://d-nb.info/972055460/34.
Повний текст джерела