@article{a69f8845b0114112a8cf6c74199455c9,
title = "Deficiency of microRNA miR-34a expands 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 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.",
author = "Choi, {Yong Jin} and Lin, {Chao Po} and Davide Risso and Sean Chen and Kim, {Thomas Aquinas} and Tan, {Meng How} and Li, {Jin Billy} and Yalei Wu and Caifu Chen and Zhenyu Xuan and Todd Macfarlan and Weiqun Peng and Lloyd, {K. C.Kent} and Kim, {Sang Yong} and Speed, {Terence P.} and Lin He",
note = "Funding Information: We thank V. Prideaux, W. Wang, R. Huang, K. N. Li, H. Aaron, J.-Y. Lee, W. Xu, J. Ong, P. Cheung, B. Zaghi, M. Chung, J. Choi, A. Li, A. Perez, W. Bao, S. Tindall, K. Zhao, K. Cui, B. Xue, O. Tam, K. Heydari, A. Valeros, M. J. Bennett, C. Cattoglio, D. Young, N. Anchell, J. A. Wood, A. Y.-F. Lee, and H. Noller for technical assistance; L. Xie, V. A. Modzelewski, and R. Song for discussion and input; T. Heidmann, J. Rossant, A. Li, V. Krizhanovsky, M. Stadtfeld, M. C. Lorincz, Y. Shinkai, D. Trono, T. Chen, and R. Jaenisch for sharing valuable reagents; P. Margolis for carefully reading the manuscript; and M. Rape and N. Patel for sharing the use of an Olympus Revolution XD spinning disk confocal microscope and a Zeiss LSM 700 confocal microscope. This work used the Vincent J. Coates Genomics Sequencing Laboratory at UC Berkeley (supported by NIH S10 instrumentation grants S10RR029668 and S10RR027303) and the computing resource provided by the Center for Systems Biology, UT Dallas. Supported by California Institute for Regenerative Medicine (CIRM) new faculty award RN2-00923-1, National Cancer Institute grant R01 CA139067, National Institute of General Medical Sciences grant R01GM114414, and a Howard Hughes Medical Institute faculty scholar award (L.H.); a CIRM predoctoral fellowship and a Cancer Research Coordinating Committee (CRCC) predoctoral fellowship (S.C.); a Siebel postdoctoral fellowship and a CIRM postdoctoral fellowship (C-P.L.); NIH grant U01MH105979 (D.R.); and the UT Dallas faculty startup fund (Z.X.). The RNA sequencing data are publicly available at the NCBI Gene Expression Omnibus with accession number GSE69484. The annotation of retrotransposons in GFF format is available as supplementary data. Publisher Copyright: {\textcopyright} 2017, American Association for the Advancement of Science. All rights reserved.",
year = "2017",
month = feb,
day = "10",
doi = "10.1126/science.aag1927",
language = "English (US)",
volume = "355",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6325",
}