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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
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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 AnimalsChromatin/chemistry/metabolismDiabetes Mellitus, Type 2/metabolism/pathologyDown-RegulationGene Expression ProfilingGenetic LociHumansInsulin-Secreting Cells/metabolismMiceRNA, Long Untranslated/metabolismRNA, Messenger/metabolismRepressor Proteins/genetics/metabolismTrans-Activators/genetics/metabolism
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PMID: 23040067
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Article (Published version) (1.1 MB) - document accessible for UNIGE members only Limited access to UNIGE
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Research group La transplantation d'îlots de Langerhans (623)
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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

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Deposited on : 2013-06-11

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