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

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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., Akerman, I., van de Bunt, M., Xie, R., Benazra, M., Nammo, T., Arnes, L., Nakić, N., García-Hurtado, J., Rodríguez-Seguí, S., Pasquali, L., Sauty-Colace, C., Beucher, A., Scharfmann, R., van Arensbergen, J., Johnson, P.R., Berry, A., Lee, C., Harkins, T., Gmyr, V., Pattou, F., Kerr-Conte, J., Piemonti, L., Berney, T., Hanley, N., Gloyn, A.L., Sussel, L., Langman, L., Brayman, K.L., Sander, M., McCarthy, M.I., 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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