Research Article

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

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Science  12 Jan 2017:
DOI: 10.1126/science.aag1927

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Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) efficiently generate all embryonic cell lineages, but rarely generate extra-embryonic cell types. We show that microRNA miR-34a deficiency expands the developmental potential of mouse pluripotent stem cells to yield both embryonic and extra-embryonic lineages and strongly induce MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with totipotent 2-cell blastomeres. miR-34a restricts the acquisition of expanded cell fate potential in pluripotent stem cells, and represses MERVL expression through transcriptional regulation, at least in part, by targeting the transcription factor Gata2. Altogether, our studies reveal a complex molecular network that defines and restricts pluripotent developmental potential, raising the tantalizing possibility of culturing bi-potential ESCs to explore the molecular basis for totipotency.

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