title: Deficiency of microRNAmiR-34aexpands cell fate potential in pluripotent stem cells.
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 microRNAmiR-34adeficiency 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-34arestricts 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.
authors.affiliation: Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA.
authors.forename: Yong Jin
authors.identifier: 0000-0002-8830-3086
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Chao-Po
authors.identifier: 0000-0002-1457-1635
authors.initials: CP
authors.lastname: Lin
authors.affiliation: Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA.
authors.forename: Davide
authors.identifier: 0000-0001-8508-5012
authors.initials: D
authors.lastname: Risso
authors.affiliation: Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA.
authors.forename: Sean
authors.identifier: 0000-0001-8343-0302
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94705, USA.
authors.forename: Thomas Aquinas
authors.initials: TA
authors.lastname: Kim
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Meng How
authors.initials: MH
authors.lastname: Tan
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jin Billy
authors.initials: JB
authors.lastname: Li
authors.affiliation: Thermo Fisher Scientific, 180 Oyster Point Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Yalei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Integrated DNA Technologies, 200 Chesapeake Drive, Redwood City, CA 94063, USA.
authors.forename: Caifu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75080, USA.
authors.forename: Zhenyu
authors.identifier: 0000-0001-9344-8493
authors.initials: Z
authors.lastname: Xuan
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
authors.forename: Todd
authors.identifier: 0000-0003-2495-9809
authors.initials: T
authors.lastname: Macfarlan
authors.affiliation: Department of Physics, George Washington University, Washington, DC 20052, USA.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Peng
authors.affiliation: Mouse Biology Program, University of California, Davis, CA 95616, USA.
authors.forename: K C Kent
authors.identifier: 0000-0002-5318-4144
authors.initials: KC
authors.lastname: Lloyd
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Statistics, University of California, Berkeley, CA 94720, USA.|Department of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.|Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Terence P
authors.identifier: 0000-0002-5403-7998
authors.initials: TP
authors.lastname: Speed
authors.affiliation: 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.
authors.forename: Lin
authors.identifier: 0000-0001-5928-1263
authors.initials: L
authors.lastname: He
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D020077:Endogenous Retroviruses / Q000235:genetics / Q000502:physiology; D005260:Female; D050989:GATA2 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014775:Virus Activation / Q000235:genetics
chemical_list: D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs