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

Yang Yang, Bei Liu, Jun Xu, Jinlin Wang, Jun Wu, Cheng Shi, Yaxing Xu, Jiebin Dong, Chengyan Wang, Weifeng Lai, Jialiang Zhu, Liang Xiong, Dicong Zhu, Xiang Li, Weifeng Yang, Takayoshi Yamauchi, Atsushi Sugawara, Zhongwei Li, Fangyuan Sun, Xiangyun LiChen Li, Aibin He, Yaqin Du, Ting Wang, Chaoran Zhao, Haibo Li, Xiaochun Chi, Hongquan Zhang, Yifang Liu, Cheng Li, Shuguang Duo, Ming Yin, Huan Shen, Juan Carlos Izpisua Belmonte, Hongkui Deng

Research output: Contribution to journalArticlepeer-review

330 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)243-257.e25
JournalCell
Volume169
Issue number2
DOIs
StatePublished - Apr 6 2017
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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