In vitro pancreas differentiation of human pluripotent stem cell line Mel1.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE134228 | GEO | 2021/10/27
REPOSITORIES: GEO
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Project description:We have identified HNF6 as an essential transcription factor for endocrine pancreatic development. HNF6 binds to and possibly regulates other isletogenesis transcription factors, driving endocrine differentiation. ATAC sequencing of control and HNF6-depleted hESC during in vitro pancreatic differentiation will help to understand the regulatory mechanisms during cell fate decisions.
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Project description:We have identified HNF6 as an essential transcription factor for endocrine pancreatic development. HNF6 binds to and possibly regulates other isletogenesis transcription factors, driving endocrine differentiation. RNA sequencing of control and HNF6-depleted hESC during in vitro pancreatic differentiation will help to understand the regulatory mechanisms during cell fate decisions.
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Project description:We have identified HNF6 as an essential transcription factor for endocrine pancreatic development. HNF6 binds to and possibly regulates other isletogenesis transcription factors, driving endocrine differentiation. ChIP sequencing of HNF6 as well as GATA6 and NKX6.1 during in vitro pancreatic differentiation will help to understand the regulatory mechanisms during cell fate decisions.
2021-10-27 | GSE131812 | GEO
Project description:Although a large set of data is available concerning organogenesis in animal models, information remains scarce on human organogenesis. In this work, we performed temporal mapping of human fetal pancreatic organogenesis using cell surface markers. We demonstrate that in the human fetal pancreas at 7 weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate either into the acinar, ductal and endocrine lineages. Development towards the acinar lineage is paralleled by a substantial increase in GP2 expression. Conversely, a subset of the multipotent GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, an early marker of endocrine differentiation. Endocrine maturation will progress by up-regulating SUSD2 and lowering ECAD levels. Finally, we show that in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work constitutes a powerful approach to more precisely define intermediate cell population during conversion of multipotent progenitors into the 3 main human pancreatic cell types (acinar, ductal and endocrine) in vivo. As such, the data pave the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.
2017-03-17 | GSE96697 | GEO
Project description:While diabetes incidence is gradually rising worldwide, novel therapeutical approaches are required in the search for a replacement of dysfunctional endocrine tissue, especially beta-cells. A promising potential lies in direct cellular reprogramming of similar cell types sharing common multipotent progenitors. With the knowledge of molecular mechanisms determining the endocrine cell fate commitment and endocrine lineage differentiation, other endocrine cells contained within the islets of Langerhans or closely related cells could be trans- or dedifferentiated either in situ or in vitro with their subsequent transplantation into the patient. NEUROD1 is a transcription factor situated on the base of the gene regulatory network of the developing endocrine precursors, directly downstream of endocrine lineage master regulator NEUROG3. While NEUROG3 initiates a rapid cascade of chromatin reorganization in numerous bivalent promoters resulting in spatiotemporal gene expression leading to differentiation of all endocrine cell subtypes from pancreatic multipotent progenitors, the role of NEUROD1 has yet to be clarified. Notably, NEUROD1 can induce neuronal program through pioneering and chromatin remodelling in other cell types. In this study, we performed advanced molecular and phenotypic analyses in early endocrine-specific Neurod1-deficient mouse model, including RNA and CUT&Tag sequencing and lightsheet microscopy, to gain insight into the NEUROD1-regulated transcription network driving endocrine lineage cell fate commitment. Besides a postnatal diabetic phenotype, disrupted endocrine differentiation and associated altered islet architecture, we observed an apparent elevation in the non-endocrine gene expression pattern and uncovered alterations in the epigenetic landscape of characteristic genes, specifically in the H3K4me3 and H3K27me3 distribution. Therefore, we provide evidence that NEUROD1 is critical player responsible for the establishment of the endocrine cell identity, which further affects endocrine development and may serve as a potent proendocrine reprogramming driver.
2023-08-17 | GSE212083 | GEO
Project description:While diabetes incidence is gradually rising worldwide, novel therapeutical approaches are required in the search for a replacement of dysfunctional endocrine tissue, especially beta-cells. A promising potential lies in direct cellular reprogramming of similar cell types sharing common multipotent progenitors. With the knowledge of molecular mechanisms determining the endocrine cell fate commitment and endocrine lineage differentiation, other endocrine cells contained within the islets of Langerhans or closely related cells could be trans- or dedifferentiated either in situ or in vitro with their subsequent transplantation into the patient. NEUROD1 is a transcription factor situated on the base of the gene regulatory network of the developing endocrine precursors, directly downstream of endocrine lineage master regulator NEUROG3. While NEUROG3 initiates a rapid cascade of chromatin reorganization in numerous bivalent promoters resulting in spatiotemporal gene expression leading to differentiation of all endocrine cell subtypes from pancreatic multipotent progenitors, the role of NEUROD1 has yet to be clarified. Notably, NEUROD1 can induce neuronal program through pioneering and chromatin remodelling in other cell types. In this study, we performed advanced molecular and phenotypic analyses in early endocrine-specific Neurod1-deficient mouse model, including RNA and CUT&Tag sequencing and lightsheet microscopy, to gain insight into the NEUROD1-regulated transcription network driving endocrine lineage cell fate commitment. Besides a postnatal diabetic phenotype, disrupted endocrine differentiation and associated altered islet architecture, we observed an apparent elevation in the non-endocrine gene expression pattern and uncovered alterations in the epigenetic landscape of characteristic genes, specifically in the H3K4me3 and H3K27me3 distribution. Therefore, we provide evidence that NEUROD1 is critical player responsible for the establishment of the endocrine cell identity, which further affects endocrine development and may serve as a potent proendocrine reprogramming driver.
2023-08-17 | GSE212082 | GEO
Project description:To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate alpha, beta and delta cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.
2006-06-30 | E-CBIL-14 | biostudies-arrayexpress
Project description:Genes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells. We used microarray analysis to detail the global changes in gene expression as Sox9 positive embryonic pancreatic progenitors differentiatiate into adult ductal cells or the endocrine lineage. GFP positive cells from Sox9-EGFP mouse pancreas were isolated by FACS at different stages of development (e10.5, e15.5, and p23) for RNA extraction and hybridization to Affymetrix microarrays. To obtain populations highly enriched in Sox9 expression, we collected only GFP Hi populations for analysis. To identify gene expression changes specific to the differentiation of progenitors to ductal cells or endocrine cells, we also isolated and analyzed the gene expression profile of GFP negative cells isolated at p23, as well as GFP positive cells isolated from Ngn3-EGFP mouse pancreas at e15.5. These two populations allow the identification of genes whose expression is associated with the newly differentiated endocrine progeny in the embryo (Ngn3-GFP positive) and adult acinar and endocrine cells at p23.
2012-08-01 | E-GEOD-34060 | biostudies-arrayexpress
Project description:This model reproduces a solution (at a=1, b=20.8, eta=1e-4) of the parameter scan in Fig. 4b of the referenced paper. Equations and other parameter values are as published. Notch signaling in competition with lateral stabilization, both mediated by cell–cell interactions, can control the cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages and yield a scattered spatial distribution of endocrine cells, major constituents of the later islets of Langerhans. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus (download from https://morpheus.gitlab.io) to simulate the time course (movie) of lineage specification in 10.000 coupled cells in the early pancreatic tissue.
2021-10-06 | MODEL2011260001 | BioModels
Project description:Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5+ stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signaling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by Partial Duct Ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) which expand 5-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality
2013-09-17 | GSE50103 | GEO