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A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation [ATAC-seq]

ABSTRACT: A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation [ATAC-seq]

PROVIDER: PRJNA705100 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13790700_1.fastq.gz	Fastqsanger.gz
	SRR13790700_2.fastq.gz	Fastqsanger.gz
	SRR13790686_1.fastq.gz	Fastqsanger.gz
	SRR13790686_2.fastq.gz	Fastqsanger.gz
	SRR13790687_1.fastq.gz	Fastqsanger.gz

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A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation [ATAC-seq]

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

A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation [RNA-seq]

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A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation

Project description:A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation

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A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation [RNA-seq]

Project description:A transcriptional and open chromatin landscape and the role of ONECUT1 in human pancreas differentiation [RNA-seq]

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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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2021-03-30 | GSE170632 | GEO

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