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Human β Cell Transcriptome Analysis Uncovers lncRNAs That Are Tissue-Specific, Dynamically Regulated, and Abnormally Expressed in Type 2 Diabetes

2012; Cell Press; Volume: 16; Issue: 4 Linguagem: Inglês

10.1016/j.cmet.2012.08.010

1932-7420

Ignasi Morán, İldem Akerman, Martijn van de Bunt, Ruiyu Xie, Marion Benazra, Takao Nammo, Luis Arnés, Nikolina Nakić, Javier García-Hurtado, Santiago A. Rodríguez‐Seguí, Lorenzo Pasquali, Claire Sauty-Colace, Anthony Beucher, Raphaël Scharfmann, J.H.J. Janssen, Paul R V Johnson, Andrew Berry, Clarence Lee, Timothy T. Harkins, Valéry Gmyr, François Pattou, Julie Kerr‐Conte, Lorenzo Piemonti, Thierry Berney, Neil A. Hanley, Anna L. Gloyn, Lori Sussel, Linda Langman, Kenneth L. Brayman, Maike Sander, Mark I. McCarthy, Philippe Ravassard, Jorge Ferrer,

Cancer-related molecular mechanisms research

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.