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Science, 10 Feb 2017: Vol. 355, Issue 6325, DOI: 10.1126/science.aag1927
Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells
Abstract
Yong Jin Choi1,*, Chao-Po Lin1,*,†, Davide Risso2,*, Sean Chen1, Thomas Aquinas Kim1, Meng How Tan3, Jin Billy Li3, Yalei Wu4, Caifu Chen5, Zhenyu Xuan6, Todd Macfarlan7, Weiqun Peng8, K. C. Kent Lloyd9, Sang Yong Kim10, Terence P. Speed11,12,13, Lin He1,†
1Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA.
1Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA.
2Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA.
3Department of Genetics, Stanford University, Stanford, CA 94305, USA.
4Thermo Fisher Scientific, 180 Oyster Point Boulevard, South San Francisco, CA 94080, USA.
5Integrated DNA Technologies, 200 Chesapeake Drive, Redwood City, CA 94063, USA.
6Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75080, USA.
7Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
8Department of Physics, George Washington University, Washington, DC 20052, USA.
9Mouse Biology Program, University of California, Davis, CA 95616, USA.
10Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
11Department of Statistics, University of California, Berkeley, CA 94720, USA.
12Department of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.
13Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
†Corresponding author.
*These authors contributed equally to this work.
Abstract
†Corresponding author.
*These authors contributed equally to this work.
Abstract
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.
논문정보
- Research article
- 2017년 02월 (BRIC 등록일 2017-02-16)
- 국외 연구진
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