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Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs

ABSTRACT: Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs

PROVIDER: PRJNA866175 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20849550.fastq.gz	Fastqsanger.gz
	SRR20849550_1.fastq.gz	Fastqsanger.gz
	SRR20849550_2.fastq.gz	Fastqsanger.gz
	SRR20849551.fastq.gz	Fastqsanger.gz
	SRR20849551_1.fastq.gz	Fastqsanger.gz

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Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs

Project description:A number of studies have reported cell heterogeneity within the developing mouse pancreas, as well as the transcriptional profiles corresponding to various cell states. The upstream mechanisms that initiate and maintain gene expression programs across cell states, however, remain largely unknown. Here, we applied single-nucleus ATAC-Seq to developing mouse pancreas to generate an atlas of chromatin accessibility, at single-cell resolution. Our goals were first, to generate an atlas of chromatin accessibility of embryonic mouse pancreas, at single-cell resolution, that can serve as a resource for the field. We aimed to provide such a resource not only for epithelial cells within the pancreas, but for non-epithelial (e.g., mesenchymal) as well. Our second goal was to identify gene regulatory networks governing cell fate transitions through integration of single-cell chromatin accessibility and gene expression data.

2023-05-18 | GSE210569 | GEO

Single cell transcriptomic and spatial landscapes of the developing human pancreas

Project description:The progress made in directed differentiation of stem cells has shown that understanding human pancreas development can provide cues for generating unlimited amounts of insulin-producing beta cells for transplantation therapy in diabetes. However, current differentiation protocols have not been successful in reproducibly generating functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single cell RNA sequencing with spatial transcriptomics at multiple developmental timepoints and revealed distinct temporal-spatial gene cascades in the developing human pancreas.

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A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas

Project description:Pancreatic and duodenal homeobox 1 (PDX1) is crucial for pancreas organogenesis, yet the dynamic changes in PDX1 binding in human or mouse developing pancreas have not been examined. To address this knowledge gap, we performed PDX1 ChIP-seq and single-cell RNA-seq using fetal human pancreata. We integrated our datasets with published datasets and revealed the dynamics of PDX1 binding and potential cell-lineage-specific PDX1 bound genes in the pancreas from fetal to adult stages. We identified a core set of developmentally conserved PDX1 bound genes that reveal the broad multifaceted role of PDX1 in pancreas development. Despite the well-known, dramatic changes in PDX1 function and expression, we found that PDX1 bound genes are largely conserved from embryonic to adult stages. This points towards a dual role of PDX1 in regulating the expression of its targets at different ages, dependent on other functionally-congruent or directly-interacting partners. We also showed that PDX1 binding is largely conserved in mouse pancreas. Together, our study reveals PDX1 targets in the developing pancreas in vivo and provides an essential resource for future studies on pancreas development.

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Methylomic trajectories in the developing human pancreas

Project description:Methylomic trajectories in the developing human pancreas

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Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs.

Project description:Numerous studies have characterized the existence of cell subtypes, along with their corresponding transcriptional profiles, within the developing mouse pancreas. The upstream mechanisms that initiate and maintain gene expression programs across cell states, however, remain largely unknown. Here, we generate single-nucleus ATAC-Sequencing data of developing murine pancreas and perform an integrated, multi-omic analysis of both chromatin accessibility and RNA expression to describe the chromatin landscape of the developing pancreas at both E14.5 and E17.5 at single-cell resolution. We identify candidate transcription factors regulating cell fate and construct gene regulatory networks of active transcription factor binding to regulatory regions of downstream target genes. This work serves as a valuable resource for the field of pancreatic biology in general and contributes to our understanding of lineage plasticity among endocrine cell types. In addition, these data identify which epigenetic states should be represented in the differentiation of stem cells to the pancreatic beta cell fate to best recapitulate in vitro the gene regulatory networks that are critical for progression along the beta cell lineage in vivo.

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Single cell transcriptomic and spatial landscapes of the developing human pancreas

Project description:Single cell transcriptomic and spatial landscapes of the developing human pancreas

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A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas

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Methylomic trajectories in the developing human pancreas

Project description:Epigenetic processes such as DNA methylation play a key role in regulating tissue-specific and temporally-appropriate patterns of gene expression during development. Our knowledge about temporal changes to the epigenome in the developing human pancreas is limited. In this study we quantified levels of DNA methylation at over 800,000 sites in 112 human fetal pancreatic samples (51 male and 61 female) spanning from 6 to 21 post conception weeks (pcw). We found dramatic changes in DNA methylation across human pancreas development, with >22% of all methylation sites displaying significant changes across developmental age, with the majority of these sites showing stable levels of DNA methylation in the mature pancreas. Sites associated with developmental changes in DNA methylation during fetal pancreas development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across pancreas development. Weighted gene correlation network analysis (WGCNA) revealed modules of co-methylated loci associated with developmental age were enriched for genes involved in maturity onset diabetes of the young (MODY) and other metabolic phenotypes. A comparison with developmentally-dynamic patterns of DNA methylation in the developing human brain revealed significant tissue specific differences between the fetal pancreas and the fetal brain. Our data confirms the prenatal period to be a time of dynamic epigenetic changes. To our knowledge, this is the most extensive study of DNA methylation patterns in human fetal pancreatic development.

2024-02-19 | GSE244636 | GEO

High-Resolution temporal profiling of developing pancreas uncovers the mechanisms of endocrine cell fate determination [ATAC-Seq]

Project description:Chromatin accessibility of endocrine progenitor cells from the e14.5 and e16.5 mouse pancreas

2018-06-05 | GSE100621 | GEO