- Home
- Featured Publications
- Center Publications
- Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks.
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks.
Citation | “Human Pancreatic Β Cell Lncrnas Control Cell-Specific Regulatory Networks.”. Cell Metabolism, pp. 400-411. . |
Center | Albert Einstein College of Medicine |
Author | Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine M Y Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-Conte, Francois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer |
Keywords | CRISPR interference, Pdx1, PLUTO, chromatin, diabetes, lncRNAs, long noncoding RNAs, pancreatic islets, transcriptional networks, type 2 diabetes |
Abstract |
Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks. |
Year of Publication |
2017
|
Journal |
Cell metabolism
|
Volume |
25
|
Issue |
2
|
Number of Pages |
400-411
|
Date Published |
12/2017
|
ISSN Number |
1932-7420
|
DOI |
10.1016/j.cmet.2016.11.016
|
Alternate Journal |
Cell Metab.
|
PMID |
28041957
|
PMCID |
PMC5300904
|
Download citation |