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

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 deficiency expands the developmental potential of mouse pluripotent stem cells, yielding both embryonic and ex...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) Vol. 355; no. 6325; p. 596
Main Authors:	Choi, Yong Jin, Lin, Chao-Po, Risso, Davide, Chen, Sean, Kim, Thomas Aquinas, Tan, Meng How, Li, Jin Billy, Wu, Yalei, Chen, Caifu, Xuan, Zhenyu, Macfarlan, Todd, Peng, Weiqun, Lloyd, K. C. Kent, Kim, Sang Yong, Speed, Terence P., He, Lin
Format:	Journal Article
Language:	English
Published:	United States American Association for the Advancement of Science 10-02-2017 The American Association for the Advancement of Science
Subjects:	Activation Animals Blastocysts Blastomeres Cell culture Cell Differentiation - genetics Cell fate Cell Lineage - genetics Cells, Cultured Coding Constraining Control Developmental plasticity Embryo cells Embryogenesis Embryonic Stem Cells - cytology Embryos Endogenous retroviruses Endogenous Retroviruses - genetics Endogenous Retroviruses - physiology Female GATA2 Transcription Factor - metabolism Gene Expression Regulation Gene Knockdown Techniques Gene regulation Genes Induced Pluripotent Stem Cells - cytology Logical Thinking Male Metabolic Networks and Pathways Mice Mice, Inbred C57BL MicroRNAs MicroRNAs - genetics MicroRNAs - physiology miRNA Molecular modelling Oct-4 protein Placenta Plasticity Pluripotency Post-transcription RESEARCH ARTICLE SUMMARY Retroviridae Ribonucleic acids RNA-mediated interference Stem cell transplantation Stem cells Transcription activation Transcription factors Transcription, Genetic Trophectoderm Virus Activation - genetics Yolk Yolk sac Zygotes
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Summary:	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 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally.
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.aag1927