Cell Metabolism - Human β Cell Transcriptome Analysis Uncovers lncRNAs That Are Tissue-Specific, Dynamically Regulated, and Abnormally Expressed in Type 2 Diabetes

Cell Metabolism - Human β Cell Transcriptome Analysis Uncovers lncRNAs That Are Tissue-Specific, Dynamically Regulated, and Abnormally Expressed in Type 2 Diabetes

Human β Cell Transcriptome Analysis Uncovers lncRNAs That Are Tissue-Specific, Dynamically Regulated, and Abnormally Expressed in Type 2 Diabetes

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Cell Metabolism, Volume 16, Issue 4, 435-448, 3 October 2012
Copyright 2012 Elsevier Inc. All rights reserved.
10.1016/j.cmet.2012.08.010

Authors

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

• Highlights
• RNA and chromatin profiling uncovers >1100 active lncRNA genes in human islet cells
• Islet lncRNAs are often cell specific and activated during endocrine differentiation
• Several islet lncRNAs exhibit conserved regulation in mouse islets
• Some lncRNAs are dysregulated in type 2 diabetes or map to susceptibility loci

Summary

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.