E-MTAB-5958
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-5958 | ExpressionAtlas | 2025-01-23
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MTAB-5958-analysis-methods.tsv | Tabular | |||
| E-MTAB-5958-analytics.tsv | Tabular | |||
| E-MTAB-5958-atlasExperimentSummary.Rdata | Rdata | |||
| E-MTAB-5958-configuration.xml | Xml | |||
| E-MTAB-5958-g3_g1-mvaPlot.png | Other |
Items per page: 5 1 - 5 of 75 |
Similar Datasets
Project description:Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo underscored important cellular plasticity in this embryonic territory. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such extended cell fate plasticity.
2021-07-01 | MODEL2105030001 | BioModels
Project description:Endoderm cells undergo a sequence of fate choices to generate insulin-secreting M-NM-2 cells. Studies of chromatin transitions during this process have been limited to the pancreatic progenitor stage that can be reconstituted from stem cells in vitro, with a gap in understanding the induction of endocrine cells. To address this, we established conditions for isolating endoderm cells, pancreatic progenitors, and endocrine cells from different staged embryos and performed genome wide analysis of the H3K27me3 mark of the repressive Polycomb complex. During the transition from endoderm to pancreas progenitors and during the transition from pancreas progenitors to endocrine cells, genes that lose the H3K27me3 mark typically encode transcriptional regulators, whereas genes that acquire the mark typically are involved in cell biology morphogenesis. Precocious depletion of the EZH2, a H3K27 methylase, at the pancreas progenitor stage enhanced the production of endocrine cells, leading to a later increase in pancreatic beta cells. Similarly, pharmacologic inhibition of EZH2 in embryonic pancreatic tissue explants and human embryonic stem cell cultures led to an increase in endocrine progenitors in vitro. These findings reveal a repeating target gene pattern in H3K27me3 dynamics and provide a means to modulate M-NM-2 cell development from stem cells. Analyzed five FACS-sorted tissues in early mouse embryo; for each tissue we sequenced H3K27me3 and input; no replicates
2014-07-28 | E-GEOD-56617 | biostudies-arrayexpress
Project description:Endoderm cells undergo a sequence of fate choices to generate insulin-secreting β cells. Studies of chromatin transitions during this process have been limited to the pancreatic progenitor stage that can be reconstituted from stem cells in vitro, with a gap in understanding the induction of endocrine cells. To address this, we established conditions for isolating endoderm cells, pancreatic progenitors, and endocrine cells from different staged embryos and performed genome wide analysis of the H3K27me3 mark of the repressive Polycomb complex. During the transition from endoderm to pancreas progenitors and during the transition from pancreas progenitors to endocrine cells, genes that lose the H3K27me3 mark typically encode transcriptional regulators, whereas genes that acquire the mark typically are involved in cell biology morphogenesis. Precocious depletion of the EZH2, a H3K27 methylase, at the pancreas progenitor stage enhanced the production of endocrine cells, leading to a later increase in pancreatic beta cells. Similarly, pharmacologic inhibition of EZH2 in embryonic pancreatic tissue explants and human embryonic stem cell cultures led to an increase in endocrine progenitors in vitro. These findings reveal a repeating target gene pattern in H3K27me3 dynamics and provide a means to modulate β cell development from stem cells.
2014-07-28 | GSE56617 | GEO
Project description:Active regulatory regions in the human embryonic pancreatic progenitors were profiled by integration of transcription factor and histone modification ChIP-seq datasets. These were obtained from pancreatic progenitor cells derived in vitro from human embryonic stem cells. The purpose of this work was to study the epigenomic mechanisms involved in pancreas development.
2013-11-15 | E-MTAB-1990 | biostudies-arrayexpress
Project description:RNA-seq of definitive endoderm and pancreatic progenitor cells derived in vitro from human pluripotent stem cells in order to study the role of transcription factor GATA6 in human pancreas development
| PRJEB22117 | ENA
Project description:Retinoic acid (RA) is required for pancreas specification in Xenopus and other vertebrates. However, the gene network that is directly induced by RA-signalling in this context remains to be defined. We identified the transcription factor Hnf1β and the Wnt-receptor Fzd4/Fzd4s as direct RA-target genes through RNA-sequencing of in vitro generated pancreatic explants. Functional analyses of Hnf1β and Fzd4/Fzd4s in programmed pancreatic explants and whole embryos revealed their requirement for pancreatic progenitor formation and differentiation. Hnf1β and Fzd4/Fzd4s thus appear to be involved in pre-patterning events of the embryonic endoderm allowing for pancreas formation.
2018-05-22 | GSE112718 | GEO
Project description:The genomic regulatory programs that underlie human organogenesis are poorly understood. Human pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer, and diabetes. We have now created maps of transcripts, active enhancers, and transcription factor networks in pancreatic multipotent progenitors obtained from human embryos, or derived in vitro from human embryonic stem cells. This revealed that artificial progenitors recapitulate salient transcriptional and epigenomic features of their natural counterparts. Using this resource, we show that TEAD1, a transcription factor controlled by Hippo signaling, is a core component of the combinatorial code of pancreatic progenitor enhancers. TEAD thus activates genes encoding regulators of signaling pathways and stage-specific transcription factors that are essential for normal pancreas development. Accordingly, chemical and genetic perturbations of TEAD and its coactivator YAP inhibited expression of known regulators such as FGFR2 and SOX9, and suppressed the proliferation and expansion of mouse and zebrafish pancreatic progenitors. These findings provide a resource of active enhancers and transcripts in human pancreatic multipotent progenitors, and uncover a central role of TEAD and YAP as signal-responsive regulators of the transcriptional program of early pancreas development.
2015-04-06 | E-MTAB-3061 | biostudies-arrayexpress
Project description:Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in stem cell biology. This knowledge will aid in the targeted differentiation and growth of stem cells, but also in the discovery of the basis of cellular plasticity and of how tissue programming can be controlled. The liver and pancreas share many aspects of their early development, being both specified in the same region of the endoderm, and, possibly, originating from a common progenitor. However, how pancreas versus liver cell fate decision occurs during embryogenesis and the molecular basis of this cellular plasticity are poorly understood. Here, we use RNA-Seq to define the molecular identity of liver and pancreas progenitors directly in mouse embryos and to investigate the mechanisms regulating the emergence of liver or pancreas as alternative fates from the endoderm. Progenitor cell-specific RNA was obtained from mouse Prox1-EGFP-labeled embryonic cells isolated by FACS at distinct developmental stages, before and after the onset of organogenesis. By integrating the temporal and spatial gene expression profiles, we found mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the non-canonical Wnt pathway as a potential developmental regulator of the pancreas versus liver fate decision, being expressed in the foregut endoderm, before the cell fate choice is made, and then maintained in pancreas progenitors but absent in hepatic progenitors. Moreover, when assayed in Xenopus embryos, the non-canonical Wnt pathway is able to promote pancreatic fate and repress hepatic fate in the endoderm, suggesting an ancient mechanism for controlling pancreas versus liver fate choice. We expect that this knowledge will be key to formulate reprogramming strategies to convert adult hepatic cells into pancreatic cells as a cell-based therapeutic approach for diabetes. We performed sequencing-based expression profiling (RNA-Seq) of hepatic and pancreatic progenitors in the mouse at two distinct developmental stages.
2013-09-11 | E-GEOD-40823 | biostudies-arrayexpress
Project description:Skin biopsies were obtained from a patient with Mitchell-Riley syndrome caused by a homozygous frame-shift mutation (c.1129C>T) in the RFX6 gene that leads to a premature stop codon (p.Arg377X). The patient suffered severe pancreatic agenesis, in common with other Mitchell-Riley syndrome patients. Fibroblasts from the biopsy were reprogrammed to generate a human induced pluripotent stem cell (hiPSC) line (MRS2-6). To assess the effects of the mutant RFX6 allele on pancreas formation and identify direct targets of the transcription factor RFX6, MRS2-6 and H9 control human embryonic stem cells (hESC) were differentiated into pancreatic progenitors. Samples were harvested for RNA isolation and whole transcriptome analysis at days 4 (definitive endoderm), 7 and 8 (gut tube), and 12 (pancreatic progenitors).
2020-03-30 | E-MTAB-6626 | biostudies-arrayexpress
Project description:deBack2012 - Lineage Specification in Pancreas Development
This model of two neighbouring pancreas precursor cells, describes the exocrine versus endocrine lineage specification process. To account for the tissue scale patterns, this couplet model has been extended to hundreds of coupled cells.
This model is described in the article:
On the role of lateral stabilization during early patterning in the pancreas
de Back W., Zhou JX, Brusch L
J. R. Soc. Interface 6 February 2013 vol. 10 no. 79 20120766
Abstract:
The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell–cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell–cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.
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2024-09-02 | BIOMD0000000435 | BioModels