Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks

Akerman, Ildem; Tu, Zhidong; Beucher, Anthony; Rolando, Delphine M Y; Sauty-Colace, Claire; Benazra, Marion; Nakic, Nikolina; Yang, Jialiang; Wang, Huan; Pasquali, Lorenzo; Moran, Ignasi; Garcia-Hurtado, Javier; Castro, Natalia; Gonzalez-Franco, Roser; Stewart, Andrew F; Bonner, Caroline; Piemonti, Lorenzo; Berney, Thierry; Groop, Leif; Kerr-Conte, Julie; Pattou, Francois; Argmann, Carmen; Schadt, Eric; Ravassard, Philippe; Ferrer, Jorge

doi:10.1016/j.cmet.2016.11.016

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Title		Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
Authors		Akerman, Ildem Tu, Zhidong Beucher, Anthony Rolando, Delphine M Y Sauty-Colace, Claire Benazra, Marion Nakic, Nikolina Yang, Jialiang Wang, Huan Pasquali, Lorenzo Moran, Ignasi Garcia-Hurtado, Javier Castro, Natalia Gonzalez-Franco, Roser Stewart, Andrew F Bonner, Caroline Piemonti, Lorenzo Berney, Thierry Groop, Leif Kerr-Conte, Julie Pattou, Francois Argmann, Carmen Schadt, Eric Ravassard, Philippe Ferrer, Jorge show all authors [1 - 25]
Published in		Cell metabolism. 2017, vol. 25, no. 2, p. 400-411
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.
Keywords		CRISPR interference — PDX1 — PLUTO — chromatin — diabetes — lncRNAs — long noncoding RNAs — pancreatic islets — transcriptional networks — type 2 diabetes
Identifiers		DOI: 10.1016/j.cmet.2016.11.016 PMID: 28041957
Full text		Article (Published version) (3.3 MB) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département de chirurgie
Research groups		La transplantation d'îlots de Langerhans (623) Transplantation et hépatologie (905)
Citation (ISO format)		AKERMAN, Ildem et al. Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks. In: Cell Metabolism, 2017, vol. 25, n° 2, p. 400-411. doi: 10.1016/j.cmet.2016.11.016 https://archive-ouverte.unige.ch/unige:93706