title: Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes.
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.
authors.affiliation: Genomic Programming of Beta Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi I Sunyer, 08036 Barcelona, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Morán
authors.forename: Ildem
authors.initials: I
authors.lastname: Akerman
authors.forename: Martijn
authors.initials: M
authors.lastname: van de Bunt
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Xie
authors.forename: Marion
authors.initials: M
authors.lastname: Benazra
authors.forename: Takao
authors.initials: T
authors.lastname: Nammo
authors.forename: Luis
authors.initials: L
authors.lastname: Arnes
authors.forename: Nikolina
authors.initials: N
authors.lastname: Nakić
authors.forename: Javier
authors.initials: J
authors.lastname: García-Hurtado
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodríguez-Seguí
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pasquali
authors.forename: Claire
authors.initials: C
authors.lastname: Sauty-Colace
authors.forename: Anthony
authors.initials: A
authors.lastname: Beucher
authors.forename: Raphael
authors.initials: R
authors.lastname: Scharfmann
authors.forename: Joris
authors.initials: J
authors.lastname: van Arensbergen
authors.forename: Paul R
authors.initials: PR
authors.lastname: Johnson
authors.forename: Andrew
authors.initials: A
authors.lastname: Berry
authors.forename: Clarence
authors.initials: C
authors.lastname: Lee
authors.forename: Timothy
authors.initials: T
authors.lastname: Harkins
authors.forename: Valery
authors.initials: V
authors.lastname: Gmyr
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.forename: Neil
authors.initials: N
authors.lastname: Hanley
authors.forename: Anna L
authors.initials: AL
authors.lastname: Gloyn
authors.forename: Lori
authors.initials: L
authors.lastname: Sussel
authors.forename: Linda
authors.initials: L
authors.lastname: Langman
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Brayman
authors.forename: Maike
authors.initials: M
authors.lastname: Sander
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravassard
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferrer
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D020869:Gene Expression Profiling; D056426:Genetic Loci; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D062085:RNA, Long Noncoding / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C478000:Glis3 protein, mouse; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators