期刊
SCIENCE
卷 355, 期 6325, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aag1927
关键词
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资金
- NIH [S10RR029668, S10RR027303, U01MH105979]
- California Institute for Regenerative Medicine (CIRM) [RN2-00923-1]
- National Cancer Institute [R01 CA139067]
- National Institute of General Medical Sciences [R01GM114414]
- Howard Hughes Medical Institute
- CIRM predoctoral fellowship
- Cancer Research Coordinating Committee (CRCC) predoctoral fellowship
- Siebel postdoctoral fellowship
- CIRM postdoctoral fellowship
- UT Dallas faculty startup fund
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.
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