title: miR-302 regulates pluripotency, teratoma formation and differentiation in stem cells via an AKT1/OCT4-dependent manner.
abstract: Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self-renewal and pluripotency, and promotes hPSC differentiation. The underlying mechanism is that the high endogenous expression of miR-302 suppresses the AKT1 expression by directly targeting its 3'UTR and subsequently maintains the pluripotent factor OCT4 at high level. Our findings reveal that miR-302 regulates OCT4 by suppressing AKT1, which provides hPSCs two characteristics related to their potential for clinical applications: the benefit of pluripotency and the hindrance of teratoma formation. More importantly, we demonstrate that miR-302 upregulation cannot lead OCT4 negative human adult mesenchymal stem cells (hMSCs) to acquire the teratoma formation in vivo. Whether miR-302 upregulation can drive hMSCs to acquire a higher differentiation potential is worthy of deep investigation.
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: H-L
authors.initials: HL
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.|Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, China.
authors.forename: J-F
authors.initials: JF
authors.lastname: Wei
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Fan
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: S-H
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: T-P
authors.initials: TP
authors.lastname: Li
authors.affiliation: Institute of Reproductive and Stem Cell Engineering, Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Central South University, Changsha, China.
authors.forename: G
authors.initials: G
authors.lastname: Lin
authors.affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Liang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Tissue Engineering Center of Chinese Academy of Medical Sciences, Beijing, China.|Peking Union Medical College Hospital, Beijing, China.
authors.forename: R-C-H
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D013724:Teratoma / Q000235:genetics / Q000473:pathology; D014162:Transfection
chemical_list: C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
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