Epigenetic control of cellular cross-talk defines organ fate and function
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE147418 | GEO | 2022/12/19
REPOSITORIES: GEO
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Project description:Epigenetic control of cellular cross-talk defines organ fate and function
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Project description:To study gene expression during endodermal organogenesis, we sought to identify genes expressed in restricted domains during organogenesis. For gene expression analysis, six morphologically distinct endodermal domains were dissected at E11.5: the esophageal region; the lung and distal tracheal region; the stomach region; the hepatic region; the dorsal and ventral pancreatic region; and the intestinal region. Through flow cytometric separation using EpCAM expression to distinguish endoderm from surrounding mesenchyme, pure populations of endoderm progenitors from the esophageal, lung, stomach, pancreatic, and intestinal regions were isolated. Expression of Liv2 was used to isolate a pure population of hepatic endoderm progenitors. Keywords: cell type comparison
2008-12-30 | GSE13040 | GEO
Project description:To study gene expression during endodermal organogenesis, we sought to identify genes expressed in restricted domains during organogenesis. For gene expression analysis, six morphologically distinct endodermal domains were dissected at E11.5: the esophageal region; the lung and distal tracheal region; the stomach region; the hepatic region; the dorsal and ventral pancreatic region; and the intestinal region. Through flow cytometric separation using EpCAM expression to distinguish endoderm from surrounding mesenchyme, pure populations of endoderm progenitors from the esophageal, lung, stomach, pancreatic, and intestinal regions were isolated. Expression of Liv2 was used to isolate a pure population of hepatic endoderm progenitors. Keywords: cell type comparison Three biological replicates each containing dissected organ domains from 10-12 pooled embryos flow cytometrically sorted to isolate endoderm were amplified using Ambion Illumina TotalPrep RNA Amplification kit and arrayed on Illumina MouseRef8 v2 chips
2010-06-24 | E-GEOD-13040 | biostudies-arrayexpress
Project description:Diverse functions of the homeodomain transcription factor BARX1 include Wnt-dependent, non-cell autonomous specification of the stomach epithelium, tracheo-bronchial septation, and Wnt-independent expansion of the spleen primordium. Tight spatio-temporal regulation of Barx1 levels in the mesentery and stomach mesenchyme suggests additional roles. To determine these functions, we forced constitutive BARX1 expression in the Bapx1 expression domain, which includes the mesentery and intestinal mesenchyme, and also examined Barx1-/- embryos in further detail. Transgenic embryos invariably showed intestinal truncation and malrotation, in part reflecting abnormal left-right patterning. Ectopic BARX1 expression did not affect intestinal epithelium, but intestinal smooth muscle developed with features typical of the stomach wall. BARX1, which is normally restricted to the developing stomach, drives robust smooth muscle expansion in this organ by promoting proliferation of myogenic progenitors at the expense of other sub-epithelial cells. Undifferentiated embryonic stomach and intestinal mesenchyme showed modest differences in mRNA expression and BARX1 was sufficient to induce much of the stomach profile in intestinal cells. However, limited binding at cis-regulatory sites implies that BARX1 may act principally through other transcription factors. Genes expressed ectopically in BARX1+ intestinal mesenchyme and reduced in Barx1-/- stomach mesenchyme include Isl1, Pitx1, Six2 and Pitx2, transcription factors known to control left-right patterning and influence smooth muscle development. The sum of evidence suggests that potent BARX1 functions in intestinal rotation and stomach myogenesis occur through this small group of intermediary transcription factors. To investigate how Barx1 regulates gut smooth muscle development in a cell-autonomous manner, we used Affymetrix arrays to profile genes enriched in wild-type stomach and BARX1-overexpressing intestinal mesenchyme, compared to wild-type intestinal mesenchyme.
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Project description:Diverse functions of the homeodomain transcription factor BARX1 include Wnt-dependent, non-cell autonomous specification of the stomach epithelium, tracheo-bronchial septation, and Wnt-independent expansion of the spleen primordium. Tight spatio-temporal regulation of Barx1 levels in the mesentery and stomach mesenchyme suggests additional roles. To determine these functions, we forced constitutive BARX1 expression in the Bapx1 expression domain, which includes the mesentery and intestinal mesenchyme, and also examined Barx1-/- embryos in further detail. Transgenic embryos invariably showed intestinal truncation and malrotation, in part reflecting abnormal left-right patterning. Ectopic BARX1 expression did not affect intestinal epithelium, but intestinal smooth muscle developed with features typical of the stomach wall. BARX1, which is normally restricted to the developing stomach, drives robust smooth muscle expansion in this organ by promoting proliferation of myogenic progenitors at the expense of other sub-epithelial cells. Undifferentiated embryonic stomach and intestinal mesenchyme showed modest differences in mRNA expression and BARX1 was sufficient to induce much of the stomach profile in intestinal cells. However, limited binding at cis-regulatory sites implies that BARX1 may act principally through other transcription factors. Genes expressed ectopically in BARX1+ intestinal mesenchyme and reduced in Barx1-/- stomach mesenchyme include Isl1, Pitx1, Six2 and Pitx2, transcription factors known to control left-right patterning and influence smooth muscle development. The sum of evidence suggests that potent BARX1 functions in intestinal rotation and stomach myogenesis occur through this small group of intermediary transcription factors.
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Project description:Environmental Enteric Dysfunction (EED) is a chronic inflammatory condition of the intestine characterized by villus blunting, compromised intestinal barrier function, and reduced nutrient absorption. Here, we show that key genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by organoid-derived intestinal epithelial cells from EED patients and cultured in nutrient deficient medium lacking niacinamide and tryptophan (-N/-T). Exposure of EED Intestine Chips to -N/-T deficiencies resulted in transcriptional changes similar to those seen in clinical EED patient samples including congruent changes in six of the top ten upregulated genes. Exposure of EED Intestine Chips or chips lined by healthy intestinal epithelium (healthy Intestine Chips) to -N/-T medium resulted in severe villus blunting and barrier dysfunction, as well as impairment of fatty acid uptake and amino acid transport.
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