De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development

被引：207

作者：

Alvarez-Dominguez, Juan R. ^{[1
,2
]}

Bai, Zhiqiang ^{[3
]}

Xu, Dan ^{[3
]}

Yuan, Bingbing ^{[1
]}

Lo, Kinyui Alice ^{[4
]}

Yoon, Myeong Jin ^{[3
]}

Lim, Yen Ching ^{[3
]}

Knoll, Marko ^{[1
]}

Slavov, Nikolai ^{[2
]}

Chen, Shuai ^{[5
]}

Chen, Peng ^{[6
]}

Lodish, Harvey F. ^{[1
,2
]}

Sun, Lei ^{[3
,4
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02142 USA

[3] Duke NUS Grad Med Sch, Cardiovasc & Metab Disorders Program, Singapore 169857, Singapore

[4] Inst Mol & Cell Biol, Singapore 138673, Singapore

[5] Nanjing Univ, Nanjing Biomed Res Inst, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China

[6] Nanyang Technol Univ, Div Bioengn, Singapore 637457, Singapore

来源：

CELL METABOLISM | 2015年 / 21卷 / 05期

基金：

新加坡国家研究基金会;

关键词：

BEIGE ADIPOCYTES; WHITE FAT; CELL; DIFFERENTIATION; OBESITY; IDENTIFICATION; ABLATION; DISTINCT; MOUSE; MICE;

D O I：

10.1016/j.cmet.2015.04.003

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：

Brown adipose tissue (BAT) protects against obesity by promoting energy expenditure via uncoupled respiration. To uncover BAT-specific long non-coding RNAs (lncRNAs), we used RNA-seq to reconstruct de novo transcriptomes of mouse brown, inguinal white, and epididymal white fat and identified similar to 1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPAR gamma, C/EBP alpha, and C/EBP beta. One of them, lnc-BATE1, is required for establishment and maintenance of BAT identity and thermogenic capacity. lnc-BATE1 inhibition impairs concurrent activation of brown fat and repression of white fat genes and is partially rescued by exogenous lnc-BATE1 with mutated siRNA-targeting sites, demonstrating a function in trans. We show that lnc-BATE1 binds heterogeneous nuclear ribonucleoprotein U and that both are required for brown adipogenesis. Our work provides an annotated catalog for the study of fat depot-selective lncRNAs and establishes lnc-BATE1 as a regulator of BAT development and physiology.

引用

页码：764 / 776

页数：13

共 48 条

[1]

Long noncoding RNAs during normal and malignant hematopoiesis [J].

Alvarez-Dominguez, Juan R. ;

Hu, Wenqian ;

Gromatzky, Austin A. ;

Lodish, Harvey F. .

INTERNATIONAL JOURNAL OF HEMATOLOGY, 2014, 99 (05) :531-541

[2]

Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation [J].

Alvarez-Dominguez, Juan R. ;

Hu, Wenqian ;

Yuan, Bingbing ;

Shi, Jiahai ;

Park, Staphany S. ;

Gromatzky, Austin A. ;

van Oudenaarden, Alexander ;

Lodish, Harvey F. .

BLOOD, 2014, 123 (04) :570-581

[3]

A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis [J].

Bostroem, Pontus ;

Wu, Jun ;

Jedrychowski, Mark P. ;

Korde, Anisha ;

Ye, Li ;

Lo, James C. ;

Rasbach, Kyle A. ;

Bostroem, Elisabeth Almer ;

Choi, Jang Hyun ;

Long, Jonathan Z. ;

Kajimura, Shingo ;

Zingaretti, Maria Cristina ;

Vind, Birgitte F. ;

Tu, Hua ;

Cinti, Saverio ;

Hojlund, Kurt ;

Gygi, Steven P. ;

Spiegelman, Bruce M. .

NATURE, 2012, 481 (7382) :463-U72

[4]

Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses [J].

Cabili, Moran N. ;

Trapnell, Cole ;

Goff, Loyal ;

Koziol, Magdalena ;

Tazon-Vega, Barbara ;

Regev, Aviv ;

Rinn, John L. .

GENES & DEVELOPMENT, 2011, 25 (18) :1915-1927

[5]

miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit [J].

Chen, Yong ;

Siegel, Franziska ;

Kipschull, Stefanie ;

Haas, Bodo ;

Froehlich, Holger ;

Meister, Gunter ;

Pfeifer, Alexander .

NATURE COMMUNICATIONS, 2013, 4

[6]

The Protein Kinase IKKε Regulates Energy Balance in Obese Mice [J].

Chiang, Shian-Huey ;

Bazuine, Merlijn ;

Lumeng, Carey N. ;

Geletka, Lynn M. ;

Mowers, Jonathan ;

White, Nicole M. ;

Ma, Jing-Tyan ;

Zhou, Jie ;

Qi, Nathan ;

Westcott, Dan ;

Delproposto, Jennifer B. ;

Blackwell, Timothy S. ;

Yull, Fiona E. ;

Saltiel, Alan R. .

CELL, 2009, 138 (05) :961-975

[7]

Identification and Importance of Brown Adipose Tissue in Adult Humans. [J].

Cypess, Aaron M. ;

Lehman, Sanaz ;

Williams, Gethin ;

Tal, Ilan ;

Rodman, Dean ;

Goldfine, Allison B. ;

Kuo, Frank C. ;

Palmer, Edwin L. ;

Tseng, Yu-Hua ;

Doria, Alessandro ;

Kolodny, Gerald M. ;

Kahn, C. Ronald .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (15) :1509-1517

[8]

Promiscuous RNA binding by Polycomb repressive complex 2 [J].

Davidovich, Chen ;

Zheng, Leon ;

Goodrich, Karen J. ;

Cech, Thomas R. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2013, 20 (11) :1250-U273

[9]

Long non-coding RNAs: new players in cell differentiation and development [J].

Fatica, Alessandro ;

Bozzoni, Irene .

NATURE REVIEWS GENETICS, 2014, 15 (01) :7-21

[10]

UCP1 Ablation Induces Obesity and Abolishes Diet-induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality [J].

Feldmann, Helena M. ;

Golozoubova, Valeria ;

Cannon, Barbara ;

Nedergaard, Jan .

CELL METABOLISM, 2009, 9 (02) :203-209

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