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Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas.

Citation
Wang, H., et al. “Insights Into Beta Cell Regeneration For Diabetes Via Integration Of Molecular Landscapes In Human Insulinomas.”. Nature Communications, p. 767.
Center Vanderbilt University Albert Einstein College of Medicine
Multicenter
Multicenter
Author Huan Wang, Aaron Bender, Peng Wang, Esra Karakose, William B Inabnet, Steven K Libutti, Andrew Arnold, Luca Lambertini, Micheal Stang, Herbert Chen, Yumi Kasai, Milind Mahajan, Yayoi Kinoshita, Gustavo Fernandez-Ranvier, Thomas C Becker, Karen K Takane, Laura A Walker, Shira Saul, Rong Chen, Donald K Scott, Jorge Ferrer, Yevgeniy Antipin, Michael Donovan, Andrew Uzilov V, Boris Reva, Eric E Schadt, Bojan Losic, Carmen Argmann, Andrew F Stewart
Abstract

Although diabetes results in part from a deficiency of normal pancreatic beta cells, inducing human beta cells to regenerate is difficult. Reasoning that insulinomas hold the "genomic recipe" for beta cell expansion, we surveyed 38 human insulinomas to obtain insights into therapeutic pathways for beta cell regeneration. An integrative analysis of whole-exome and RNA-sequencing data was employed to extensively characterize the genomic and molecular landscape of insulinomas relative to normal beta cells. Here, we show at the pathway level that the majority of the insulinomas display mutations, copy number variants and/or dysregulation of epigenetic modifying genes, most prominently in the polycomb and trithorax families. Importantly, these processes are coupled to co-expression network modules associated with cell proliferation, revealing candidates for inducing beta cell regeneration. Validation of key computational predictions supports the concept that understanding the molecular complexity of insulinoma may be a valuable approach to diabetes drug discovery.Diabetes results in part from a deficiency of functional pancreatic beta cells. Here, the authors study the genomic and epigenetic landscapes of human insulinomas to gain insight into possible pathways for therapeutic beta cell regeneration, highlighting epigenetic genes and pathways.

Year of Publication
2017
Journal
Nature communications
Volume
8
Issue
1
Number of Pages
767
Date Published
12/2017
ISSN Number
2041-1723
DOI
10.1038/s41467-017-00992-9
Alternate Journal
Nat Commun
PMID
28974674
PMCID
PMC5626682
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