Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming
Transcriptomics Dataset
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General Information
AccessionGSE50386
TitleEpigenomic plasticity enables human pancreatic alpha to beta cell reprogramming
DescriptionInsulin-secreting cells and glucagon-secreting cells maintain physiological blood glucose levels, and their malfunction drives diabetes development. Using ChIP sequencing and RNA sequencing analysis, we determined the epigenetic and transcriptional landscape of human pancreatic , , and exocrine cells. We found that, compared with exocrine and cells, differentiated cells exhibited many more genes bivalently marked by the activating H3K4me3 and repressing H3K27me3 histone modifications. This was particularly true for cell signature genes involved in transcriptional regulation. Remarkably, thousands of these genes were in a monovalent state in cells, carrying only the activating or repressing mark. Our epigenomic findings suggested that to cell reprogramming could be promoted by manipulating the histone methylation signature of human pancreatic islets. Indeed, we show that treatment of cultured pancreatic islets with a histone methyltransferase inhibitor leads to colocalization of both glucagon and insulin and glucagon and insulin promoter factor 1 (PDX1) in human islets and colocalization of both glucagon and insulin in mouse islets. Thus, mammalian pancreatic islet cells display cell-typespecific epigenomic plasticity, suggesting that epigenomic manipulation could provide a path to cell reprogramming and novel cell replacement-based therapies for diabetes.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50386
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE50386
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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