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

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

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Title		Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes
Authors		Morán, Ignasi Akerman, Ildem van de Bunt, Martijn Xie, Ruiyu Benazra, Marion Nammo, Takao Arnes, Luis Nakić, Nikolina García-Hurtado, Javier Rodríguez-Seguí, Santiago Pasquali, Lorenzo Sauty-Colace, Claire Beucher, Anthony Scharfmann, Raphael van Arensbergen, Joris Johnson, Paul R Berry, Andrew Lee, Clarence Harkins, Timothy Gmyr, Valery Pattou, François Kerr-Conte, Julie Piemonti, Lorenzo Berney, Thierry Hanley, Neil Gloyn, Anna L Sussel, Lori Langman, Linda Brayman, Kenneth L Sander, Maike McCarthy, Mark I Ravassard, Philippe Ferrer, Jorge show all authors [1 - 33]
Published in		Cell Metabolism. 2012, vol. 16, no. 4, p. 435-48
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
Identifiers		DOI: 10.1016/j.cmet.2012.08.010 PMID: 23040067
Full text		Article (Published version) (1.1 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de chirurgie
Research group		La transplantation d'îlots de Langerhans (623)
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. 435-48. https://archive-ouverte.unige.ch/unige:28510