Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Robust differentiation of human enteroendocrine cells from intestinal stem cells

ABSTRACT: Enteroendocrine (EE) cells are the most abundant hormone-producing cells in humans and are critical regulators of energy homeostasis and gastrointestinal function. Challenges in converting human intestinal stem cells (ISCs) into functional EE cells, ex vivo, have limited progress in elucidating their role in disease pathogenesis and in harnessing their therapeutic potential. To address this, we employed small molecule targeting of key transcriptional regulators, GATA4, JNK and FOXO1, known to mediate endodermal development and hormone production, together with directed differentiation of human ISCs from the duodenum and rectum. We observed marked induction of EE cell differentiation and gut-derived expression and secretion of SST, 5HT, GIP, GLP-1 and PYY upon treatment with various combinations of three small molecules: rimonabant, SP600125 and AS1842856. Robust differentiation strategies capable of driving human EE cell differentiation is a critical step towards understanding these essential cells and the development of cell-based therapeutics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178342 | GEO | 2021/11/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell RNA-sequencing reveals distinct populations of glucagon-like peptide-1 producing cells in the mouse upper small intestine

Project description:Enteroendocrine L-cells release hormones that control metabolism and appetite and are targets under investigation for the treatment of diabetes and obesity. Understanding L-cell diversity and expression profiles is critical for identifying target receptors that will translate into altered hormone secretion. We performed single cell RNA sequencing of mouse L-cells from the upper small intestine to distinguish cellular populations, revealing that L-cells form 3 major clusters: a group with typical characteristics of classical L-cells, including high expression of Gcg and Pyy; a cell type overlapping with Gip-expressing K-cells; and a unique cluster expressing Tph1 and Pzp that was predominantly located in duodenal villi and co-produced 5HT. Expression of G-protein coupled receptors differed between clusters, suggesting the cell types are differentially regulated, and would be differentially targetable. Our findings support the emerging concept that many enteroendocrine cell populations are highly overlapping, with individual cells producing a range of peptides previously assigned to distinct cell types.

2017-12-15 | GSE108108 | GEO

Peptidomics profiling of biopsies from the human jejunum before and after gastrectomy

Project description:Profiling of the human jejunum peptidome before and after total gastrectomy. The study compares the peptidome of jejunum using intact mass spectrometry and database searching. These peptides included most gut hormones including proglucagon derived peptides, PYY, GIP, Motilin somatostatin and neurotensin amongst others.

2019-02-15 | PXD011498 | Pride

Profiling of Esg genomic binding in the Drosophila midgut with DamID

Project description:Tissue stem cells divide asymmetrically to self-renew and generate differentiated progeny to maintain tissue homeostasis. Escargot (Esg) is a transcriptional repressor that is expressed in multiple stem cell populations in Drosophila melanogaster. Reduced esg function in intestinal stem cells (ISCs) causes a loss of ISCs and a biased differentiation of the daughter enteroblasts (EBs) toward the enteroendocrine (EE) cell fate. Loss of esg leads to an upregulation of differentiation factors and reduced Notch activity within EBs, indicating that Esg is a pivotal regulator of homeostasis in the intestine, supporting self-renewal to maintain a healthy stem cell pool as well as differentiation of progenitor cells. To identify potential transcriptional targets that mediate these phenotypes, in vivo DamID was used to generate the data deposited herein. 3 biological relicates were performed for Esg (with one dye-swap).

2014-11-18 | E-GEOD-55226 | biostudies-arrayexpress

Peptidomics profiling of the murine gut after vertical sleeve gastrectomy

Project description:Profiling of the murine peptidome along the gastrointestinal tract and pancreas in vertical sleeve gastrectomy and sham operated mice. The study compares the peptidome of various portions of the GI tract using intact mass spectrometry and database searching. These peptides included most gut hormones including proglucagon derived peptides, PYY, GIP, somatostatin, neurotensin amongst others.

2019-02-09 | PXD011455 | Pride

Proliferation and differentiation of intestinal stem cells depends on the zinc finger transcription factor BCL11/Chronophage

Project description:The molecular programs that drive proliferation and differentiation of intestinal stem cells (ISCs) are essential for organismal fitness. Notch signalling regulates the binary fate decision of ISCs, favouring enterocyte commitment when Notch activity is high and enteroendocrine cell (EE) fate when activity is low. However, the gene regulatory mechanisms that underlie this process on an organ scale remain poorly understood. Here, we find that the expression of the C2H2-type zinc-finger transcription factor Chronophage (Cph), homologous to mammalian BCL11, increases specifically along the ISC-to-EE lineage when Notch is inactivated. We show that the expression of Cph is regulated by the Achaete-Scute Complex (AS-C) gene, scute, which directly binds to multiple sites within the Cph locus to promote its expression. Our genetic and single-cell RNA sequencing experiments demonstrate that Cph maintains the ISC and EE populations and is necessary to remodel the transcriptome of progenitor cells with low Notch activity. By identifying and functionally validating Cph target genes, we uncover a novel role for sugar free frosting (sff) in directing proliferative and lineage commitment steps of ISCs. Our findings provide mechanistic insight into how Cph maintains intestinal epithelial homeostasis, and together with our evolutionary analysis of Cph/BCL11, suggests that it may represent a general mechanism used by adult somatic stem cells in other tissues to balance proliferation and differentiation.

2024-09-06 | GSE276185 | GEO

Proliferation and differentiation of intestinal stem cells depends on the zinc finger transcription factor BCL11/Chronophage

2024-10-28 | GSE280439 | GEO

Nutrient-driven dedifferentiation of enteroendocrine cells promotes adaptive intestinal growth

Project description:Post-developmental organ resizing improves organismal fitness under constantly changing nutrient environments. Although stem cell abundance is a fundamental determinant of adaptive resizing, our understanding of its underlying mechanisms remains primarily limited to the regulation of stem cell division. Here, we demonstrate that nutrient fluctuation induces dedifferentiation in the Drosophila adult midgut to drive adaptive intestinal growth. From lineage tracing and single-cell RNA sequencing, we identify a subpopulation of enteroendocrine (EE) cells that convert into functional intestinal stem cells (ISCs) in response to dietary glucose and amino acids by activating the JAK-STAT pathway. Genetic ablation of EE-derived ISCs severely impairs ISC expansion and midgut growth despite the retention of resident ISCs, and in silico modeling further indicates that EE dedifferentiation enables an efficient increase in the midgut cell number while maintaining epithelial cell composition. Our findings identify a physiologically induced dedifferentiation that ensures ISC expansion during adaptive organ growth in concert with nutrient conditions.

2023-08-12 | GSE207662 | GEO

Single-cell sequencing of enteroendocrine cells (EEs) in Drosophila midgut.

Project description:Enteroendocrine cells (EEs) in the intestinal epithelium have important endocrine functions, yet this cell lineage exhibits great local and regional variations that have hampered detailed characterization of EE subtypes. Through single cell RNA-sequencing analysis, combined with a collection of neuropeptide/receptor knock-in strains, here we provide a comprehensive analysis of cellular diversity, spatial distribution and transcription factor (TF) code of EEs in adult Drosophila midgut. We identify 10 major EE subtypes that totally produced 14 different classes of hormone peptides. Each EE on average co-produces 2-5 different classes of hormone peptides. Functional screen with subtype-enriched TFs suggests a combinatorial TF code that controls EE cell diversity, with class-specific TFs Mirr and Ptx1that respectively define two major classes of EEs, and regional TFs such as Esg, Drm, Exex and Fer1that further define regional EE identity. Our single-cell data should greatly facilitate Drosophila modeling of EE differentiation and function.

2019-11-04 | GSE132274 | GEO

Profiling of Esg genomic binding in the Drosophila midgut with DamID

2014-11-18 | GSE55226 | GEO

RNAseq of Aging Drosophila ISCs

Project description:Tissue homeostasis requires long-term lineage fidelity of somatic stem cells. Whether and how age-related changes in somatic stem cells impact the faithful execution of lineage decisions remains largely unknown. Here, we address this question using genome-wide chromatin accessibility and transcriptome analysis as well as single cell RNA-seq to explore stem cell intrinsic changes in the aging Drosophila intestine. These studies indicate that in stem cells of old flies, promoters of Polycomb (Pc) target genes become differentially accessible, resulting in the increased expression of enteroendocrine (EE) cell specification genes. Consistently, we find age related changes in the composition of the EE progenitor cell population in aging intestines, as well as a significant increase in the proportion of EE-specified ISCs and progenitors in aging flies. We further confirm that Pc-mediated chromatin regulation is a critical determinant of EE cell specification in the Drosophila intestine. Pc is required to maintain expression of stem cell genes while ensuring repression of differentiation and specification genes. Our results identify Pc group proteins as central regulators of lineage identity in the intestinal epithelium and highlight the impact of age-related decline in chromatin regulation on tissue homeostasis.

2021-04-02 | GSE157794 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data