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Science. 2017 Feb 10;355(6325). pii: eaag1927. doi: 10.1126/science.aag1927. Epub 2017 Jan 12.

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

Author information

1
Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA.
2
Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA. lhe@berkeley.edu newcplin@gmail.com.
3
Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA.
4
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
5
Thermo Fisher Scientific, 180 Oyster Point Boulevard, South San Francisco, CA 94080, USA.
6
Integrated DNA Technologies, 200 Chesapeake Drive, Redwood City, CA 94063, USA.
7
Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75080, USA.
8
Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
9
Department of Physics, George Washington University, Washington, DC 20052, USA.
10
Mouse Biology Program, University of California, Davis, CA 95616, USA.
11
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
12
Department of Statistics, University of California, Berkeley, CA 94720, USA.
13
Department of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.
14
Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

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.

Comment in

PMID:
28082412
PMCID:
PMC6138252
DOI:
10.1126/science.aag1927
[Indexed for MEDLINE]
Free PMC Article

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