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Cell Metab. 2012 Oct 3;16(4):435-48. doi: 10.1016/j.cmet.2012.08.010.

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

Author information

1
Genomic Programming of Beta Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi I Sunyer, 08036 Barcelona, Spain.

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.

PMID:
23040067
PMCID:
PMC3475176
DOI:
10.1016/j.cmet.2012.08.010
[Indexed for MEDLINE]
Free PMC Article

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