Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells.
Yong Jin ChoiChao-Po LinDavide RissoSean ChenThomas Aquinas KimMeng How TanJin Billy LiYalei WuCaifu ChenZhenyu XuanTodd S MacfarlanWeiqun PengKevin C Kent LloydSang Yong KimTerence P SpeedLin HePublished in: Science (New York, N.Y.) (2017)
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.
Keyphrases
- pluripotent stem cells
- cell fate
- single cell
- cell proliferation
- long non coding rna
- transcription factor
- induced pluripotent stem cells
- cell therapy
- poor prognosis
- human health
- embryonic stem cells
- stem cells
- gene expression
- endothelial cells
- risk assessment
- mesenchymal stem cells
- climate change
- replacement therapy
- smoking cessation