Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks

Article Article scientifique Article Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks eng 2017 author Akerman Ildem author Tu Zhidong author Beucher Anthony author Rolando Delphine M Y author Sauty-Colace Claire author Benazra Marion author Nakic Nikolina author Yang Jialiang author Wang Huan 631400 author Pasquali Lorenzo author Moran Ignasi author Garcia-Hurtado Javier author Castro Natalia author Gonzalez-Franco Roser author Stewart Andrew F author Bonner Caroline author Piemonti Lorenzo author Berney Thierry 63319 author Groop Leif author Kerr-Conte Julie author Pattou Francois author Argmann Carmen author Schadt Eric author Ravassard Philippe author Ferrer Jorge 400-411 10.1016/j.cmet.2016.11.016 28041957 1550-4131 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. CRISPR interference PDX1 PLUTO chromatin diabetes lncRNAs long noncoding RNAs pancreatic islets transcriptional networks type 2 diabetes Dewey 617 57 Département de chirurgie 222 false 357 La transplantation d'îlots de Langerhans 623 562 Transplantation et hépatologie 905 Cell metabolism 25 2 d0ff2751-6e59-4bea-8324-aff6b7af1471 Article (Published version) Public cell_meta_hum_pancrea_cell_incrnas.pdf 3414069 application/pdf CC BY openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks	Cell metabolism			2017	561	326

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Wang, Huan