Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells

被引：133

作者：

Choi, Yong Jin ^{[1
]}

Lin, Chao-Po ^{[1
]}

Risso, Davide ^{[2
]}

Chen, Sean ^{[1
]}

Kim, Thomas Aquinas ^{[1
]}

Tan, Meng How ^{[3
]}

Li, Jin Billy ^{[3
]}

Wu, Yalei ^{[4
]}

Chen, Caifu ^{[5
]}

Xuan, Zhenyu ^{[6
]}

Macfarlan, Todd ^{[7
]}

Peng, Weiqun ^{[8
]}

Lloyd, K. C. Kent ^{[9
]}

Kim, Sang Yong ^{[10
]}

Speed, Terence P. ^{[11
,12
,13
]}

He, Lin ^{[1
]}

机构：

[1] Univ Calif Berkeley, Div Cellular & Dev Biol, Dept Mol & Cell Biol, Berkeley, CA 94705 USA

[2] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA

[3] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[4] Thermo Fisher Sci, 180 Oyster Point Blvd, San Francisco, CA 94080 USA

[5] Integrated DNA Technol, 200 Chesapeake Dr, Redwood City, CA 94063 USA

[6] Univ Texas Dallas, Dept Mol & Cell Biol, Richardson, TX 75080 USA

[7] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA

[8] George Washington Univ, Dept Phys, Washington, DC 20052 USA

[9] Univ Calif Davis, Mouse Biol Program, Davis, CA 95616 USA

[10] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[11] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA

[12] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia

[13] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3052, Australia

来源：

SCIENCE | 2017年 / 355卷 / 6325期

关键词：

STAGE MOUSE BLASTOMERES; GENE-EXPRESSION; MUERV-L; EMBRYOS; DIFFERENTIATION; P53; CONTRIBUTES; APOPTOSIS; ENDODERM; BIOLOGY;

D O I：

10.1126/science.aag1927

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) efficiently generate all embryonic cell lineages but rarely generate extraembryonic cell types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse pluripotent stem cells, yielding both embryonic and extraembryonic lineages and strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features of totipotent two-cell blastomeres. miR-34a restricts the acquisition of expanded cell fate potential in pluripotent stem cells, and it represses MERVL expression through transcriptional regulation, at least in part by targeting the transcription factor Gata2. Our studies reveal a complex molecular network that defines and restricts pluripotent developmental potential in cultured ESCs and iPSCs.

引用

页数：11

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