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Role of transcription factor ONECUT1 (HNF6) during in vitro pancreatic differentiation of human pluripotent stem cells [RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE135416 | GEO | 2021/10/27

REPOSITORIES: GEO

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Role of transcription factor ONECUT1 (HNF6) during in vitro pancreatic differentiation of human pluripotent stem cells [ATAC-seq]

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.

2021-10-27 | GSE131816 | GEO

Role of transcription factors ONECUT1 (HNF6), GATA6 and NKX6.1 during in vitro pancreatic differentiation of human pluripotent stem cells.

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

Mutations and variants of ONECUT1 in diabetes

Project description:Genes involved in distinct diabetes types suggest shared disease mechanisms. We show that rare ONECUT1 coding variants cause monogenic recessive diabetes (neonatal or very early-onset, syndromic) in two unrelated patients, and monogenic dominant diabetes (early adult-onset) in heterozygous relatives of these and 13 additional unrelated cases. Patients heterozygous for rare ONECUT1 coding variants define a subgroup of T2D with early-onset diabetes and other features. In addition, common regulatory ONECUT1 variants are associated with multifactorial T2D. Directed differentiation of human pluripotent stem cells to the pancreatic lineage revealed that loss of ONECUT1 impairs pancreatic progenitor formation and a subsequent endocrine program. We uncovered that ONECUT1 activates the pro-endocrine genes NKX6.1 and NKX2.2 through binding to their cis-regulatory elements. Globally, ONECUT1-directed gene transcription occurs in association with major islet transcription factors, at clusters of pancreas- and endocrine-specific enhancers within open chromatin. ONECUT1 regulates a transcriptional and epigenetic machinery critical for proper endocrine pancreatic development, involved in a spectrum of diabetes, monogenic recessive and dominant, and multifactorial.

2021-11-03 | PXD018887 | Pride

Role of transcription factor ONECUT1 (HNF6) during in vitro pancreatic differentiation of human pluripotent stem cells [RNA-seq]

Project description:Role of transcription factor ONECUT1 (HNF6) during in vitro pancreatic differentiation of human pluripotent stem cells [RNA-seq]

| PRJNA558795 | ENA

Role of transcription factor ONECUT1 (HNF6) during in vitro pancreatic differentiation of human pluripotent stem cells [ATAC-seq]

Project description:Role of transcription factor ONECUT1 (HNF6) during in vitro pancreatic differentiation of human pluripotent stem cells [ATAC-seq]

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Pathophysiological role of hepatocyte nuclear factor 6 (HNF6) during cholestatic liver injury

Project description:Animal models of parenchymal liver injury by bile duct ligation (BDL) and all forms of liver diseases including neonatal hepatitis and clinical obstructive cholangiopathies such as biliary atresia have the pathological features of cholestasis and liver dysfunction. Hepatocyte nuclear factors 6 (HNF6) is important to the transcriptional regulation, expression and function of essential hepatic genes involved in the differentiated as well as the adaptive response to liver injury. Using HNF6 conditional knock out mice where HNF6 is functionally deleted in the liver, we established that HNF6 is required for proper liver function of cholesterol clearance, improvement of cholestasis and hepatocyte regeneration. Enhancing HNF6 expression in wild type mice also diminished hepatic apoptosis and fibrosis. In this proposal, we propose to further characterize the biological function of HNF6 by testing the HYPOTHESIS that HNF6 direct transcriptional regulation of antiapoptotic and antifibrotic pathways contributes to hepatoprotection during bile duct injury. This hypothesis will be tested in two specific aims.

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Role of transcription factors ONECUT1 (HNF6), GATA6 and NKX6.1 during in vitro pancreatic differentiation of human pluripotent stem cells.

Project description:Role of transcription factors ONECUT1 (HNF6), GATA6 and NKX6.1 during in vitro pancreatic differentiation of human pluripotent stem cells.

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Identification of Hnf6 binding sites in male and female mouse liver

Project description:∼40,000 HNF6 binding sites were identified in mouse liver chromatin, including several thousand sites showing significant differences in level of HNF6 binding between male and female mouse liver. These sex-biased HNF6 binding sites showed strong enrichment for sex-biased DNase hypersensitive sites and for proximity to genes showing local sex-biased chromatin marks and a corresponding sex-biased expression. ~90% of genome-wide CUX2 binding sites identified previously in female mouse liver (Conforto TL, Zhang Y, Sherman J, Waxman DJ., Mol Cell Biol. 2012;32(22):4611-4627) were also bound by HNF6, giving evidence for genome-wide competition between HNF6 and CUX2 for chromatin binding in female mouse liver. These HNF6/CUX2 common binding sites were enriched for genomic regions more accessible in male than in female mouse liver chromatin, and showed strongest enrichment for male-biased genes, suggesting HNF6 displacement by CUX2 as a mechanism to explain the observed CUX2 repression of male-biased genes in female liver. However, HNF6 binding was sex-independent at a majority of its binding sites, and peak regions of HNF6 binding were frequently associated with co-binding by multiple other liver transcription factors, consistent with HNF6 playing a global regulatory role in both male and female liver.

2015-07-28 | GSE60014 | GEO

In vitro pancreas differentiation of human pluripotent stem cell line Mel1.

Project description:We have identified an essential transcription factor for endocrine pancreatic development, that binds to and possibly regulates other isletogenesis transcription factors, driving endocrine differentiation.

2021-10-27 | GSE134228 | GEO

Identification of Hnf6 binding sites in male and female mouse liver

2015-07-28 | E-GEOD-60014 | biostudies-arrayexpress

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