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Series GSE50386 Query DataSets for GSE50386
Status Public on Aug 28, 2013
Title Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Insulin-secreting β cells and glucagon-secreting α 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 α, β, and exocrine cells. We found that, compared with exocrine and β cells, differentiated α cells exhibited many more genes bivalently marked by the activating H3K4me3 and repressing H3K27me3 histone modifications. This was particularly true for β cell signature genes involved in transcriptional regulation. Remarkably, thousands of these genes were in a monovalent state in β cells, carrying only the activating or repressing mark. Our epigenomic findings suggested that α to β 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-type–specific epigenomic plasticity, suggesting that epigenomic manipulation could provide a path to cell reprogramming and novel cell replacement-based therapies for diabetes.
 
Overall design Pancreatic islets were collected post-mortem from 6 human donors and subjected to FACS to separate populations of alpha, beta, and exocrine cells. Depending on the availability of resulting material, sorted islet cell populations were used for H3K4me3, H3K27me3 ChIP-seq, or RNA-seq analysis. All ChIP-seq samples have a corresponding input from the same sample.
 
Contributor(s) Bramswig NC, Everett LJ, Schug J, Dorrell C, Liu C, Luo Y, Streeter PR, Naji A, Grompe M, Kaestner KH
Citation(s) 23434589
Submission date Aug 28, 2013
Last update date Mar 20, 2019
Contact name Logan J Everett
E-mail loganjeverett@gmail.com
Organization name North Carolina State University
Department Biological Sciences / Genetics
Lab Trudy Mackay
Street address 112 Derieux Place
City Raleigh
State/province NC
ZIP/Postal code 27606
Country USA
 
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (44)
GSM1217919 CITH053_Exocrine_H3K4me3
GSM1217920 CITH053_Alpha_Input
GSM1217921 CITH068_Alpha_Input
Relations
BioProject PRJNA217397
SRA SRP029281

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE50386_RAW.tar 156.7 Mb (http)(custom) TAR (of BED)
Raw data are available in SRA
Processed data provided as supplementary file

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