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Epigenomic plasticity enables human pancreatic α to β cell reprogramming
Nuria C Bramswig1, Logan J Everett, Jonathan Schug
1Department of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
The Journal of Clinical Investigation
|February 26, 2013
Summary
Scientists discovered that manipulating histone methylation in pancreatic islets could reprogram alpha cells to become more like beta cells. This finding offers a potential new avenue for diabetes cell replacement therapies.
Area of Science:
- Endocrinology
- Epigenetics
- Cell Biology
Background:
- Pancreatic alpha and beta cells regulate blood glucose; their dysfunction causes diabetes.
- Understanding the epigenetic regulation of these cell types is crucial for diabetes research.
Purpose of the Study:
- To investigate the epigenetic and transcriptional differences between human pancreatic alpha, beta, and exocrine cells.
- To explore the potential of epigenomic manipulation for cell reprogramming in pancreatic islets.
Main Methods:
- ChIP sequencing and RNA sequencing were employed to analyze the epigenetic and transcriptional landscapes.
- Histone methyltransferase inhibitors were used to treat cultured pancreatic islets.
Main Results:
- Differentiated alpha cells showed significantly more bivalently marked genes (H3K4me3 and H3K27me3) compared to beta and exocrine cells.
- Many beta cell signature genes were in a monovalent state in beta cells.
- Inhibitor treatment induced co-localization of glucagon and insulin, and PDX1 in human islets, and glucagon and insulin in mouse islets.
Conclusions:
- Human pancreatic islet cells exhibit cell-type-specific epigenomic plasticity.
- Targeting histone methylation signatures may facilitate alpha to beta cell reprogramming.
- Epigenomic manipulation presents a promising strategy for developing cell replacement therapies for diabetes.
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