title: A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming.
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.
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Jingyang
authors.initials: J
authors.lastname: Guan
authors.affiliation: 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.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: Junqing
authors.initials: J
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Gaofan
authors.initials: G
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
authors.affiliation: 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.
authors.forename: Susu
authors.initials: S
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Linlin
authors.initials: L
authors.lastname: Su
authors.affiliation: Beijing Vitalstar Biotechnology Co., Ltd., Beijing 100012, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D000067470:Cellular Reprogramming Techniques; D055808:Drug Discovery; D004622:Embryo, Mammalian / Q000166:cytology; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects