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Cell. 2015 Dec 17;163(7):1678-91. doi: 10.1016/j.cell.2015.11.017. Epub 2015 Dec 10.

A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming.

Author information

1
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, 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. Electronic address: yangzhao@pku.edu.cn.
2
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, 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; Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, College of Life Sciences, Peking University, Beijing 100871, China.
3
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, 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.
4
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, 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.
5
Beijing Vitalstar Biotechnology Co., Ltd., Beijing 100012, China.
6
Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Center for Molecular and Translational Medicine, 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

Somatic cells can be reprogrammed into pluripotent stem cells (PSCs) by using pure chemicals, providing a different paradigm to study somatic reprogramming. However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. We now show that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to chemically-induced (Ci)PSCs, a unique route that fundamentally differs from the pathway of transcription factor-induced reprogramming. Moreover, precise manipulation of the cell fate transition in a step-wise manner through the XEN-like state allows us to identify small-molecule boosters and establish a robust chemical reprogramming system with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a promising approach to manipulate cell fates.

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PMID:
26686652
DOI:
10.1016/j.cell.2015.11.017
[Indexed for MEDLINE]
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