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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Endogenous Retroviruses / genetics
  • Endogenous Retroviruses / physiology
  • Female
  • GATA2 Transcription Factor / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Induced Pluripotent Stem Cells / cytology*
  • Male
  • Metabolic Networks and Pathways
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Transcription, Genetic
  • Virus Activation / genetics


  • GATA2 Transcription Factor
  • Gata2 protein, mouse
  • MIRN34a microRNA, mouse
  • MicroRNAs