Human pancreatic β cell lncRNAs control cell-specific regulatory networks

Research output: Contribution to journalArticlepeer-review

Authors

  • 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

Colleges, School and Institutes

External organisations

  • Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai
  • Imperial College London
  • Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut du cerveau et de la moelle (ICM) – Hôpital Pitié-Salpêtrière, Boulevard de l’Hôpital
  • Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
  • Germans Trias i Pujol University Hospital and Research Institute and Josep Carreras Leukaemia Research Institute
  • Genomic Programming of Beta Cells Laboratory, Institut d’Investigacions Biomediques August Pi I Sunyer (IDIBAPS)
  • Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai
  • European Genomic Institute for Diabetes
  • Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute
  • Cell Isolation and Transplantation Center, University of Geneva
  • Department of Clinical Sciences, Lund University Diabetes Centre, Lund University

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.

Details

Original languageEnglish
Pages (from-to)400-411
Number of pages12
JournalCell Metabolism
Volume25
Issue number2
Early online date29 Dec 2016
Publication statusPublished - 7 Feb 2017

Keywords

  • Chromatin, Diabetes Mellitus, Type 2, Gene Expression Regulation, Gene Knockdown Techniques, Gene Regulatory Networks, Homeodomain Proteins, Humans, Insulin, Insulin-Secreting Cells, Multigene Family, Phenotype, RNA, Long Noncoding, RNA, Messenger, Trans-Activators, Transcription Factors, Transcription, Genetic, Journal Article