title: Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.
abstract: Of all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their ability to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic placental tissues in vivo. Here, we show that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues. Notably, a single mouse EPS cell shows widespread chimeric contribution to both embryonic and extraembryonic lineages in vivo and permits generating single-EPS-cell-derived mice by tetraploid complementation. Furthermore, human EPS cells exhibit interspecies chimeric competency in mouse conceptuses. Our findings constitute a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China; Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China; Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing, 100044, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Shi
authors.affiliation: Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yaxing
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Jiebin
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Jialiang
authors.initials: J
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authors.affiliation: Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Liang
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authors.lastname: Xiong
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China; Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Dicong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Xiang
authors.initials: X
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authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
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authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
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authors.lastname: Sugawara
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Zhongwei
authors.initials: Z
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authors.affiliation: College of Animal Science and Technology, Hebei University, Baoding 071002, China.
authors.forename: Fangyuan
authors.initials: F
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authors.affiliation: College of Animal Science and Technology, Hebei University, Baoding 071002, China.
authors.forename: Xiangyun
authors.initials: X
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authors.affiliation: Institute of Molecular Medicine, Peking University, PKU-Tsinghua U Joint Center for Life Sciences, Beijing 100871, China.
authors.forename: Chen
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authors.affiliation: Institute of Molecular Medicine, Peking University, PKU-Tsinghua U Joint Center for Life Sciences, Beijing 100871, China.
authors.forename: Aibin
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authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Yaqin
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authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
authors.forename: Ting
authors.initials: T
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authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
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authors.initials: C
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authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China.
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authors.initials: H
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authors.affiliation: Laboratory of Stem Cells, Development and Reproductive Medicine, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
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authors.affiliation: Laboratory of Stem Cells, Development and Reproductive Medicine, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
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authors.affiliation: Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; School of Life Sciences, Center for Statistical Science, Peking University, Beijing 100871, China; Center for Bioinformatics, Peking University, Beijing 100871, China.
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authors.affiliation: Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing, 100044, China. Electronic address: rmivf@sina.com.
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authors.lastname: Shen
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA. Electronic address: belmonte@salk.edu.
authors.forename: Juan Carlos Izpisua
authors.initials: JCI
authors.lastname: Belmonte
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China; Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China. Electronic address: hongkui_deng@pku.edu.cn.
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mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D002678:Chimera / Q000378:metabolism; D004115:Dimethindene / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D051379:Mice; D008911:Minocycline / Q000737:chemistry / Q000494:pharmacology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism
chemical_list: D007202:Indicators and Reagents; D004115:Dimethindene; D000071137:Poly (ADP-Ribose) Polymerase-1; D008911:Minocycline
keywords: chimeric ability; embryonic and extraembryonic developmental potentials; interspecies chimeric competency; single-cell derived chimeras