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

Ignasi Morán; Ildem 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 Ferrer

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

Ignasi Morán, Ildem 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 GmyrFrançois 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 Ferrer

Research output: Contribution to journal › Article › peer-review

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. © 2012 Elsevier Inc.

Original language	English
Pages (from-to)	435-448
Number of pages	13
Journal	Cell Metabolism
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2012.08.010
Publication status	Published - 3 Oct 2012

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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., ... Ferrer, J. (2012). Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. Cell Metabolism, 16(4), 435-448. https://doi.org/10.1016/j.cmet.2012.08.010

@article{406dcbcc2d224ade9888420b28e8a0fa,

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. {\textcopyright} 2012 Elsevier Inc.",

author = "Ignasi Mor{\'a}n and Ildem Akerman and {Van De Bunt}, Martijn and Ruiyu Xie and Marion Benazra and Takao Nammo and Luis Arnes and Nikolina Naki{\'c} and Javier Garc{\'i}a-Hurtado and Santiago Rodr{\'i}guez-Segu{\'i} and Lorenzo Pasquali and Claire Sauty-Colace and Anthony Beucher and Raphael Scharfmann and {Van Arensbergen}, Joris and Johnson, {Paul R.} and Andrew Berry and Clarence Lee and Timothy Harkins and Valery Gmyr and Fran{\c c}ois Pattou and Julie Kerr-Conte and Lorenzo Piemonti and Thierry Berney and Neil Hanley and Gloyn, {Anna L.} and Lori Sussel and Linda Langman and Brayman, {Kenneth L.} and Maike Sander and McCarthy, {Mark I.} and Philippe Ravassard and Jorge Ferrer",

year = "2012",

month = oct,

day = "3",

doi = "10.1016/j.cmet.2012.08.010",

language = "English",

volume = "16",

pages = "435--448",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "4",

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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, PR, Berry, A, Lee, C, Harkins, T, Gmyr, V, Pattou, F, Kerr-Conte, J, Piemonti, L, Berney, T, Hanley, N, Gloyn, AL, Sussel, L, Langman, L, Brayman, KL, Sander, M, McCarthy, MI, Ravassard, P & Ferrer, J 2012, 'Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes', Cell Metabolism, vol. 16, no. 4, pp. 435-448. https://doi.org/10.1016/j.cmet.2012.08.010

TY - JOUR

T1 - Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes

AU - Morán, Ignasi

AU - Akerman, Ildem

AU - Van De Bunt, Martijn

AU - Xie, Ruiyu

AU - Benazra, Marion

AU - Nammo, Takao

AU - Arnes, Luis

AU - Nakić, Nikolina

AU - García-Hurtado, Javier

AU - Rodríguez-Seguí, Santiago

AU - Pasquali, Lorenzo

AU - Sauty-Colace, Claire

AU - Beucher, Anthony

AU - Scharfmann, Raphael

AU - Van Arensbergen, Joris

AU - Johnson, Paul R.

AU - Berry, Andrew

AU - Lee, Clarence

AU - Harkins, Timothy

AU - Gmyr, Valery

AU - Pattou, François

AU - Kerr-Conte, Julie

AU - Piemonti, Lorenzo

AU - Berney, Thierry

AU - Hanley, Neil

AU - Gloyn, Anna L.

AU - Sussel, Lori

AU - Langman, Linda

AU - Brayman, Kenneth L.

AU - Sander, Maike

AU - McCarthy, Mark I.

AU - Ravassard, Philippe

AU - Ferrer, Jorge

PY - 2012/10/3

Y1 - 2012/10/3

N2 - 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. © 2012 Elsevier Inc.

AB - 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. © 2012 Elsevier Inc.

U2 - 10.1016/j.cmet.2012.08.010

DO - 10.1016/j.cmet.2012.08.010

M3 - Article

SN - 1550-4131

VL - 16

SP - 435

EP - 448

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -

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

Abstract

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