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

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

PROVIDER: PRJNA545075 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9133940_1.fastq.gz	Fastqsanger.gz
	SRR9133940_2.fastq.gz	Fastqsanger.gz
	SRR9133950_1.fastq.gz	Fastqsanger.gz
	SRR9133950_2.fastq.gz	Fastqsanger.gz
	SRR9133960_1.fastq.gz	Fastqsanger.gz

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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.

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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]

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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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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.

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