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: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: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: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.
This model is hosted on BioModels Database
and identified by: MODEL1211010000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000435 | BioModels
Project description:Pancreatic differentiation and specification of lineages is a tightly controlled process involving a interconnected network of transcriptional regulation. Although more knowledge on human pancreatic development is accumulating, the precise role of many transcription factors is only described in mouse. Therefore, it is of great interest to expand our knowledge using alternative model systems such as pancreatic in vitro differentiation of human pluripotent stem cells. Here, we provide stage-specific data from RNA-, ChIP-, and ATAC-sequencing to dissect transcriptional and regulatory mechanisms during pancreatic development. Transcriptome and open chromatin maps of pancreas differentiation from human pluripotent stem cells provide a stage-specific pattern of known pancreas transcription factors and determine ONECUT1 as a crucial regulator in pancreas progenitors. Moreover, our data suggest that ONECUT1 is also involved in preparing pancreatic progenitors for later endocrine specification.Our approach of dissecting the transcriptional and regulatory mechanisms revealed an important role for the specific key player ONECUT1 and will help to better understand human development and disease.
2021-10-27 | GSE167602 | GEO
Project description:Pancreatic differentiation and specification of lineages is a tightly controlled process involving a interconnected network of transcriptional regulation. Although more knowledge on human pancreatic development is accumulating, the precise role of many transcription factors is only described in mouse. Therefore, it is of great interest to expand our knowledge using alternative model systems such as pancreatic in vitro differentiation of human pluripotent stem cells. Here, we provide stage-specific data from RNA-, ChIP-, and ATAC-sequencing to dissect transcriptional and regulatory mechanisms during pancreatic development. Transcriptome and open chromatin maps of pancreas differentiation from human pluripotent stem cells provide a stage-specific pattern of known pancreas transcription factors and determine ONECUT1 as a crucial regulator in pancreas progenitors. Moreover, our data suggest that ONECUT1 is also involved in preparing pancreatic progenitors for later endocrine specification.Our approach of dissecting the transcriptional and regulatory mechanisms revealed an important role for the specific key player ONECUT1 and will help to better understand human development and disease.
2021-10-27 | GSE167596 | GEO
Project description:A small molecule, AT7867, promotes proliferation of human pluripotent stem cell-derived pancreatic progenitor cells (PPCs), yet detailed mechanisms of its proliferative effect were not fully understood. Here, we performed cell-based siRNA screening on a subset of genes to reveal that WNT7B is a growth factor of human PPCs as previously shown in mouse pancreas development. Although recombinant proteins had no in vitro activity, feeder cell lines stably expressing Wnt7a or Wnt7b enhanced PPC proliferation. Further analyses showed that canonical Wnt signaling pathway was not affected by AT7867 treatment as well as Wnt7a and Wnt7b. Knockdown of a non-canonical Wnt pathway component, PKCα, and its downstream substrate, MARCKS, blocked PPC proliferation suggesting a requirement of this pathway. Phosphoproteome analysis revealed that AT7867 inhibited Yin Yang 1 (YY1) phosphorylation at Ser118, which directly or indirectly regulated expression of WNT7B in PPCs. Taken together, non-canonical Wnt signaling mediated by WNT7B plays a critical role for the expansion of human PPC population that is a promising alternative cell source to generate β cells for the cure of diabetes.
2021-07-01 | PXD018221 | JPOST Repository
Project description:A small molecule, AT7867, promotes proliferation of human pluripotent stem cell-derived pancreatic progenitor cells (PPCs), yet detailed mechanisms of its proliferative effect were not fully understood. Here, we performed cell-based siRNA screening on a subset of genes to reveal that WNT7B is a growth factor of human PPCs as previously shown in mouse pancreas development. Although recombinant proteins had no in vitro activity, feeder cell lines stably expressing Wnt7a or Wnt7b enhanced PPC proliferation. Further analyses showed that canonical Wnt signaling pathway was not affected by AT7867 treatment as well as Wnt7a and Wnt7b. Knockdown of a non-canonical Wnt pathway component, PKCα, and its downstream substrate, MARCKS, blocked PPC proliferation suggesting a requirement of this pathway. Phosphoproteome analysis revealed that AT7867 inhibited Yin Yang 1 (YY1) phosphorylation at Ser118, which directly or indirectly regulated expression of WNT7B in PPCs. Taken together, non-canonical Wnt signaling mediated by WNT7B plays a critical role for the expansion of human PPC population that is a promising alternative cell source to generate β cells for the cure of diabetes.
2022-03-27 | PXD018222 | JPOST Repository
Project description:Understanding the pancreatic developmental process is instrumental to tackle diabetes, allowing improvements of in vitro differentiation protocols aimed at producing of functional β-cells for transplantation. Here, we investigate the role of Glucocorticoid Receptor (GR) signaling in the earliest stages of pancreas development decisions in both mice and humans. Previous reports suggest that glucocorticoids do not play a significant role in mouse pancreas development before the second transition. In this study, we demonstrate that, under physiological conditions, the GR is selectively active in pro-acinar cells of the mouse embryonic pancreas from E11.5 and on. It is silenced in early-stage bipotent and endocrine progenitors, and its expression is reactivated upon endocrine commitment. Ectopic GR activation in mouse pancreatic explants globally commits progenitors to the acinar lineage. In sharp contrast, GR activation in in vitro-derived human pancreatic multipotent progenitors promotes commitment to the endocrine lineage, inducing the expression of novel genes associated with human embryonic pancreatic bipotential and endocrine progenitors. A combined epigenomic and single-cell transcriptomic screen suggests that these novel marker genes could play important roles in human pancreas development. Taken together, our findings position the GR pathway as an endogenous developmental modulator of early-stage pancreatic progenitor cell differentiation. We also demonstrate that glucocorticoids can bias in vitro-derived human pancreatic progenitor cell commitment toward the endocrine lineage and provide insights into the underlying transcriptional mechanisms potentially involved.
2025-04-30 | GSE237280 | GEO
Project description:Metabolism is vital to cellular function and tissue homeostasis during human lung development. In utero, embryonic pluripotent stem cells undergo endodermal differentiation towards a lung progenitor cell fate that can be mimicked in vitro using induced human pluripotent stem cells (hiPSCs) to study genetic mutations. To identify differences between wild type and surfactant protein B (SFTPB)-deficient cell lines during endoderm specification towards lung, we used an untargeted metabolomics approach to evaluate the developmental changes in metabolites. We found that the metabolites most enriched during the differentiation from pluripotent stem cell to lung progenitor cell, regardless of cell line, were sphingomyelins and phosphatidylcholines, two important lipid classes in fetal lung development. The SFTPB mutation had no metabolic impact on early endodermal lung development. The identified metabolite signatures during lung progenitor cell differentiation may be utilized as biomarkers for normal embryonic lung development.
2021-06-29 | ST002055 | MetabolomicsWorkbench
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