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Cell. 2017 Apr 6;169(2):243-257.e25. doi: 10.1016/j.cell.2017.02.005.

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.

Author information

1
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.
2
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.
3
Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
4
Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing, 100044, China.
5
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, College of Life Sciences, Peking University, Beijing 100871, China.
6
Beijing Vitalstar Biotechnology, Beijing 100012, China.
7
College of Animal Science and Technology, Hebei University, Baoding 071002, China.
8
Institute of Molecular Medicine, Peking University, PKU-Tsinghua U Joint Center for Life Sciences, Beijing 100871, China.
9
Laboratory of Stem Cells, Development and Reproductive Medicine, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
10
School of Life Sciences, Tsinghua University, Beijing 100084, China.
11
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.
12
Institute of Zoology, Chinese Academy Sciences, Beijing 100101, China.
13
Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing, 100044, China. Electronic address: rmivf@sina.com.
14
Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA. Electronic address: belmonte@salk.edu.
15
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.

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.

KEYWORDS:

chimeric ability; embryonic and extraembryonic developmental potentials; interspecies chimeric competency; single-cell derived chimeras

PMID:
28388409
PMCID:
PMC5679268
DOI:
10.1016/j.cell.2017.02.005
[Indexed for MEDLINE]
Free PMC Article

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