Human Pancreatic ß Cell lncRNAs Control Cell-Specific Regulatory Networks
Akerman, Ildem (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Tu, Zhidong (Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai)
Beucher, Anthony (Imperial College London)
Rolando, Delphine M. Y. (Imperial College London)
Sauty-Colace, Claire (Institut du cerveau et de la moelle. Hôpital Pitié-Salpêtrière)
Benazra, Marion (Institut du cerveau et de la moelle. Hôpital Pitié-Salpêtrière)
Nakic, Nikolina (Imperial College London)
Yang, Jialiang (Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai)
Wang, Huan (Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai)
Pasquali, Lorenzo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Moran, Ignasi (Imperial College London)
Garcia Hurtado, Javier (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Castro, Natalia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Gonzalez Franco, Roser (Imperial College London)
Stewart, Andrew F. (Icahn School of Medicine at Mount Sinai (Nova York, Estats Units d'Amèrica). Diabetes, Obesity, and Metabolism Institute)
Bonner, Caroline (European Genomic Institute for Diabetes)
Piemonti, Lorenzo (Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute)
Berney, Thierry (Cell Isolation and Transplantation Center, University of Geneva)
Groop, Leif (Department of Clinical Sciences, Lund University Diabetes Centre)
Kerr-Conte, Julie (European Genomic Institute for Diabetes)
Pattou, Francois (European Genomic Institute for Diabetes)
Argmann, Carmen (Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai)
Schadt, Eric (Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai)
Ravassard, Phillipe (Institut du cerveau et de la moelle. Hôpital Pitié-Salpêtrière)
Ferrer, Jorge (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic ß cells. ß 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 ß cell gene regulation and diabetes, the function of b cell lncRNAs remains largely unknown. In this study, we investigated the function of b 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 ß cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key ß 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 ß cell-specific transcription factor networks.
Grants:	European Commission 667191 Ministerio de Economía y Competitividad FU2014-54284-R
Note:	Altres ajuts: WT/WT101033
Note:	Altres ajuts: NIH-BCBC/2U01 DK072473-06
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Cell metabolism, Vol. 25 (february 2017) , p. 400-411

DOI: 10.1016/j.cmet.2016.11.016
PMID: 28041957

13 p, 3.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles