Programming human pluripotent stem cells into white and brown adipocytes

被引：187

作者：

Ahfeldt, Tim ^{[1
,2
,3
]}

Schinzel, Robert T. ^{[1
,2
,3
,4
]}

Lee, Youn-Kyoung ^{[1
,2
,3
]}

Hendrickson, David ^{[1
,5
]}

Kaplan, Adam ^{[1
,2
,3
]}

Lum, David H. ^{[6
,7
]}

Camahort, Raymond ^{[1
,2
,3
]}

Xia, Fang ^{[1
,2
,3
]}

Shay, Jennifer ^{[1
,2
,3
]}

Rhee, Eugene P. ^{[3
,5
]}

Clish, Clary B. ^{[5
]}

Deo, Rahul C. ^{[8
,9
,10
]}

Shen, Tony ^{[1
,2
]}

Lau, Frank H. ^{[2
,3
]}

Cowley, Alicia ^{[1
,2
]}

Mowrer, Greg ^{[2
,3
]}

Al-Siddiqi, Heba ^{[1
,2
,3
,11
]}

Nahrendorf, Matthias ^{[12
,13
]}

Musunuru, Kiran ^{[1
,5
,14
]}

Gerszten, Robert E. ^{[3
,5
]}

Rinn, John L. ^{[1
,5
]}

Cowan, Chad A. ^{[1
,2
,3
,5
]}

机构：

[1] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[2] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[4] Free Univ Berlin, Fachbereich Biol, Inst Biol Mikrobiol, D-14195 Berlin, Germany

[5] 7 Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA

[6] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA

[7] Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84112 USA

[8] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[10] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[11] Qatar Fdn, Div Res, Doha, Qatar

[12] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[13] Harvard Univ, Sch Med, Boston, MA 02114 USA

[14] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

来源：

NATURE CELL BIOLOGY | 2012年 / 14卷 / 02期

关键词：

ADIPOSE-TISSUE; PPAR-GAMMA; TRANSCRIPTIONAL CONTROL; DIFFERENTIATION; GENE; DERIVATION; IDENTIFICATION; FIBROBLASTS; VIVO;

D O I：

10.1038/ncb2411

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%-90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.

引用

页码：209 / 219

页数：11

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