Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes

Ignasi Morán, Ildem Akerman, Martijn Van De Bunt, Ruiyu Xie, Marion Benazra, Takao Nammo, Luis Arnes, Nikolina Nakić, Javier García-Hurtado, Santiago Rodríguez-Seguí, Lorenzo Pasquali, Claire Sauty-Colace, Anthony Beucher, Raphael Scharfmann, Joris Van Arensbergen, Paul R. Johnson, Andrew Berry, Clarence Lee, Timothy Harkins, Valery GmyrFrançois Pattou, Julie Kerr-Conte, Lorenzo Piemonti, Thierry Berney, Neil Hanley, Anna L. Gloyn, Lori Sussel, Linda Langman, Kenneth L. Brayman, Maike Sander, Mark I. McCarthy, Philippe Ravassard, Jorge Ferrer

Research output: Contribution to journalArticlepeer-review

Abstract

A significant portion of the genome is transcribed as long noncoding RNAs (lncRNAs), several of which are known to control gene expression. The repertoire and regulation of lncRNAs in disease-relevant tissues, however, has not been systematically explored. We report a comprehensive strand-specific transcriptome map of human pancreatic islets and β cells, and uncover >1100 intergenic and antisense islet-cell lncRNA genes. We find islet lncRNAs that are dynamically regulated and show that they are an integral component of the β cell differentiation and maturation program. We sequenced the mouse islet transcriptome and identify lncRNA orthologs that are regulated like their human counterparts. Depletion of HI-LNC25, a β cell-specific lncRNA, downregulated GLIS3 mRNA, thus exemplifying a gene regulatory function of islet lncRNAs. Finally, selected islet lncRNAs were dysregulated in type 2 diabetes or mapped to genetic loci underlying diabetes susceptibility. These findings reveal a new class of islet-cell genes relevant to β cell programming and diabetes pathophysiology.

Original languageEnglish
Pages (from-to)435-448
Number of pages14
JournalCell Metabolism
Volume16
Issue number4
DOIs
Publication statusPublished - Oct 3 2012

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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