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

Published inCell metabolism, vol. 16, no. 4, p. 435-448
Publication date2012
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.

Keywords
  • Animals
  • Chromatin/chemistry/metabolism
  • Diabetes Mellitus, Type 2/metabolism/pathology
  • Down-Regulation
  • Gene Expression Profiling
  • Genetic Loci
  • Humans
  • Insulin-Secreting Cells/metabolism
  • Mice
  • RNA, Long Untranslated/metabolism
  • RNA, Messenger/metabolism
  • Repressor Proteins/genetics/metabolism
  • Trans-Activators/genetics/metabolism
Citation (ISO format)
MORÁN, Ignasi et al. Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. In: Cell metabolism, 2012, vol. 16, n° 4, p. 435–448. doi: 10.1016/j.cmet.2012.08.010
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ISSN of the journal1550-4131
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