Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks

被引：179

作者：

Akerman, Ildem ^{[1
,2
,3
]}

Tu, Zhidong ^{[4
]}

Beucher, Anthony ^{[1
]}

Rolando, Delphine M. Y. ^{[1
]}

Sauty-Colace, Claire ^{[5
]}

Benazra, Marion ^{[5
]}

Nakic, Nikolina ^{[1
]}

Yang, Jialiang ^{[4
]}

Wang, Huan ^{[4
]}

Pasquali, Lorenzo ^{[3
,6
,7
,8
]}

Moran, Ignasi ^{[1
]}

Garcia-Hurtado, Javier ^{[2
,3
]}

Castro, Natalia ^{[2
,3
]}

Gonzalez-Franco, Roser ^{[1
]}

Stewart, Andrew F. ^{[9
]}

Bonner, Caroline ^{[10
]}

Piemonti, Lorenzo ^{[11
]}

Berney, Thierry ^{[12
]}

Groop, Leif ^{[13
]}

Kerr-Conte, Julie ^{[10
]}

Pattou, Francois ^{[10
]}

Argmann, Carmen ^{[4
]}

Schadt, Eric ^{[4
]}

Ravassard, Philippe ^{[5
]}

Ferrer, Jorge ^{[1
,2
,3
]}

机构：

[1] Imperial Coll London, Sect Epigen & Dis, Dept Med, London W12 0NN, England

[2] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Genom Programming Beta Cells Lab, Barcelona 08036, Spain

[3] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid 28029, Spain

[4] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[5] UPMC Univ Paris 06, Hop Pitie Salpetriere,ICM, Sorbonne Univ,CNRS, INSERM, F-75013 Paris, France

[6] Germans Trias & Pujol Univ Hosp, Badalona 08916, Spain

[7] Res Inst, Badalona 08916, Spain

[8] Josep Carreras Leukaemia Res Inst, Badalona 08916, Spain

[9] Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, New York, NY 10029 USA

[10] INSERM, UMR 1190, European Genom Inst Diabet, F-59800 Lille, France

[11] Ist Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, Italy

[12] Univ Geneva, Cell Isolat & Transplantat Ctr, CH-12114 Geneva 4, Switzerland

[13] Lund Univ, Diabet Ctr, Dept Clin Sci, S-20502 Lund, Sweden

来源：

CELL METABOLISM | 2017年 / 25卷 / 02期

基金：

英国惠康基金; 欧盟地平线“2020”;

关键词：

LONG NONCODING RNAS; GENE-EXPRESSION; TRANSCRIPTIONAL LANDSCAPE; ENDOCRINE PANCREAS; REVEALS; DIFFERENTIATION; EVOLUTION; LINCRNAS; PDX-1; LINE;

D O I：

10.1016/j.cmet.2016.11.016

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic beta cells. beta cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in beta cell gene regulation and diabetes, the function of beta cell lncRNAs remains largely unknown. In this study, we investigated the function of beta cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate b cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key b cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of beta cell-specific transcription factor networks.

引用

页码：400 / 411

页数：12

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