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; K C Kent Lloyd; Sang Yong Kim; Terence P Speed; Lin He

doi:10.1126/science.aag1927

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.

Authors

Yong Jin Choi¹, Chao-Po Lin², Davide Risso³, Sean Chen¹, Thomas Aquinas Kim¹, Meng How Tan⁴, Jin Billy Li⁴, Yalei Wu⁵, Caifu Chen⁶, Zhenyu Xuan⁷, Todd Macfarlan⁸, Weiqun Peng⁹, K C Kent Lloyd¹⁰, Sang Yong Kim¹¹, Terence P Speed^{12

13

14}, Lin He²

Affiliations

¹ Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA.
² Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA. lhe@berkeley.edu newcplin@gmail.com.
³ Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA.
⁴ Department of Genetics, Stanford University, Stanford, CA 94305, USA.
⁵ Thermo Fisher Scientific, 180 Oyster Point Boulevard, South San Francisco, CA 94080, USA.
⁶ Integrated DNA Technologies, 200 Chesapeake Drive, Redwood City, CA 94063, USA.
⁷ Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75080, USA.
⁸ Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
⁹ Department of Physics, George Washington University, Washington, DC 20052, USA.
¹⁰ Mouse Biology Program, University of California, Davis, CA 95616, USA.
¹¹ Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
¹² Department of Statistics, University of California, Berkeley, CA 94720, USA.
¹³ Department of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.
¹⁴ Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

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.

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding