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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks

Author

  • Ildem Akerman
  • Zhidong Tu
  • Anthony Beucher
  • Delphine M Y Rolando
  • Claire Sauty-Colace
  • Marion Benazra
  • Nikolina Nakic
  • Jialiang Yang
  • Huan L. 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

Summary, in English

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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017-02-07

Language

English

Pages

400-411

Publication/Series

Cell Metabolism

Volume

25

Issue

2

Document type

Journal article

Publisher

Cell Press

Topic

  • Endocrinology and Diabetes
  • Medical Genetics

Keywords

  • chromatin
  • CRISPR interference
  • diabetes
  • lncRNAs
  • long noncoding RNAs
  • pancreatic islets
  • PDX1
  • PLUTO
  • transcriptional networks
  • type 2 diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1550-4131