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

Item Type:	Article
Title:	Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes.
Creators Name:	Morán, I. and Akerman, I. and van de Bunt, M. and Xie, R. and Benazra, M. and Nammo, T. and Arnes, L. and Nakić, N. and García-Hurtado, J. and Rodríguez-Seguí, S. and Pasquali, L. and Sauty-Colace, C. and Beucher, A. and Scharfmann, R. and van Arensbergen, J. and Johnson, P.R. and Berry, A. and Lee, C. and Harkins, T. and Gmyr, V. and Pattou, F. and Kerr-Conte, J. and Piemonti, L. and Berney, T. and Hanley, N. and Gloyn, A.L. and Sussel, L. and Langman, L. and Brayman, K.L. and Sander, M. and McCarthy, M.I. and Ravassard, P. and Ferrer, J.
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:	Chromatin, DNA-Binding Proteins, Type 2 Diabetes Mellitus, Down-Regulation, Gene Expression Profiling, Genetic Loci, Insulin-Secreting Cells, Long Noncoding RNA, Messenger RNA, Repressor Proteins, Trans-Activators, Trans-Activators / Metabolism, Animals, Mice
Source:	Cell Metabolism
ISSN:	1550-4131
Publisher:	Cell Press
Volume:	16
Number:	4
Page Range:	435-48
Date:	3 October 2012
Official Publication:	https://doi.org/10.1016/j.cmet.2012.08.010
PubMed:	View item in PubMed

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