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

Yong Jin Choi, Chao Po Lin, Davide Risso, Sean Chen, Thomas Aquinas Kim, Meng How Tan, Jin Billy Li, Yalei Wu, Caifu Chen, Zhenyu Xuan, Todd Macfarlan, Weiqun Peng, Kevin C K Lloyd, Sang Yong Kim, Terence P. Speed, Lin He

Research output: Contribution to journalArticle

62 Scopus citations

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.

Original languageEnglish (US)
Article numbereaag1927
JournalScience
Volume355
Issue number6325
DOIs
StatePublished - Feb 10 2017

ASJC Scopus subject areas

  • Medicine(all)
  • General

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    Choi, Y. J., Lin, C. P., Risso, D., Chen, S., Kim, T. A., Tan, M. H., Li, J. B., Wu, Y., Chen, C., Xuan, Z., Macfarlan, T., Peng, W., Lloyd, K. C. K., Kim, S. Y., Speed, T. P., & He, L. (2017). Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells. Science, 355(6325), [eaag1927]. https://doi.org/10.1126/science.aag1927