Human Pancreatic beta Cell lncRNAs Control Cell-Specific Regulatory Networks

Akerman Ildem; Tu Zhidong; Beucher AnthonyRolando Delphine M. Y.Sauty-Colace ClaireBenazra MarionNakic NikolinaYang JialiangWang HuanPasquali LorenzoMoran IgnasiGarcia-Hurtado JavierCastro NataliaGonzalez-Franco RoserStewart Andrew F.Bonner CarolinePiemonti LorenzoBerney ThierryGroop LeifKerr-Conte JuliePattou FrancoisArgmann CarmenSchadt EricRavassard PhilippeFerrer Jorge

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Human Pancreatic beta Cell lncRNAs Control Cell-Specific Regulatory Networks

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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.

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《Cell metabolism》 |2017年第2期|400-411|共12页
作者
Akerman Ildem; Tu Zhidong; Beucher AnthonyRolando Delphine M. Y.Sauty-Colace ClaireBenazra MarionNakic NikolinaYang JialiangWang HuanPasquali LorenzoMoran IgnasiGarcia-Hurtado JavierCastro NataliaGonzalez-Franco RoserStewart Andrew F.Bonner CarolinePiemonti LorenzoBerney ThierryGroop LeifKerr-Conte JuliePattou FrancoisArgmann CarmenSchadt EricRavassard PhilippeFerrer Jorge;
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Imperial Coll London, Sect Epigen & Dis, Dept Med, London W12 0NN, England;

Lund Univ, Diabet Ctr, Dept Clin Sci, S-20502 Lund, Sweden;

INSERM, UMR 1190, European Genom Inst Diabet, F-59800 Lille, FranceIcahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USAUPMC Univ Paris 06, Hop Pitie Salpetriere,ICM, Sorbonne Univ,CNRS, INSERM, F-75013 Paris, FranceIst Sci San Raffaele, Diabet Res Inst HSR DRI, I-20132 Milan, ItalyUniv Geneva, Cell Isolat & Transplantat Ctr, CH-12114 Geneva 4, SwitzerlandCtr Invest Biomed Red Diabet & Enfermedades Metab, Madrid 28029, SpainInst Invest Biomed August Pi & Sunyer IDIBAPS, Genom Programming Beta Cells Lab, Barcelona 08036Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, New York, NY 10029 USA;

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1. Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites. [J] . Gerrish K, Gannon M, Shih DHenderson EStoffel MWright CVStein R The Journal of biological chemistry . 2000,第5期

机译：Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites.
2. Human T-cell leukaemia/lymphoma virus type 1 syncytium formation is regulated in a cell-specific manner by ICAM-1, ICAM-3 and VCAM-1 and can be inhibited by antibodies to integrin beta2 or beta7. [J] . Daenke S, McCracken SA, Booth S The Journal of General Virology: A Federation of European Miorobiological Societies Journal . 1999,第6期

机译：Human T-cell leukaemia/lymphoma virus type 1 syncytium formation is regulated in a cell-specific manner by ICAM-1, ICAM-3 and VCAM-1 and can be inhibited by antibodies to integrin beta2 or beta7.
3. Cell-specific cytotoxicity of human pancreatic adenocarcinoma cells using rat insulin promoter thymidine kinase-directed gene therapy. [J] . Tirone TA, Wang XP, Templeton NSLee TNguyen LFisher WBrunicardi FC World Journal of Surgery: Official Journal of the Societe Internationale de Chirurgie, Collegium Internationale Chirurgiae Digestivae, and of the International Association of Endocrine Surgeons . 2004,第8期

机译：Cell-specific cytotoxicity of human pancreatic adenocarcinoma cells using rat insulin promoter thymidine kinase-directed gene therapy.
4. Real-time Simultaneous Measurement of Pancreatic β Cell Electrophysiology and Fluorescent Bioimaging Based on High-resolution Thin-film Transistor Microelectrode Arrays [C] . Dongchen Zhu, Anne-Claire Eiler, Satoshi Ihida, センサ·マイクロマシンと応用システムシンポジウム;電気学会;集積化MEMSシンポジウム . -1

机译：Real-time Simultaneous Measurement of Pancreatic β Cell Electrophysiology and Fluorescent Bioimaging Based on High-resolution Thin-film Transistor Microelectrode Arrays
5. Retraction Notice: Jinshui He Xu Zhang Chaowei Lian Jinzhi Wu Yanling Fang Xiaoling Ye. Exendin-4 prevented pancreatic beta cells from apoptosis in (Type I) diabetic mouse via keap1-Nrf2 signaling [O] . 2020

机译：Retraction Notice: Jinshui He Xu Zhang Chaowei Lian Jinzhi Wu Yanling Fang Xiaoling Ye. Exendin-4 prevented pancreatic beta cells from apoptosis in (Type I) diabetic mouse via keap1-Nrf2 signaling
6. TGF-β of lung cancer microenvironment upregulates B7H1 and GITRL expression in dendritic cells and is associated with regulatory T cell generation [O] . XIAO YAN NI, HUA XIU SUI, YAO LIU, 2012

机译：TGF-beta of lung cancer microenvironment upregulates B7H1 and GITRL expression in dendritic cells and is associated with regulatory T cell generation

Human Pancreatic beta Cell lncRNAs Control Cell-Specific Regulatory Networks

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