单位：[1]Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Science, Tsinghua University, Beijing 100084, China[2]School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China[3]Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA[4]Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA[5]MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, BNRist, and Department of Automation, Tsinghua University, Beijing 100084, China[6]Department of Operations and Information Management, China-Japan Friendship Hospital, Beijing 100029, China[7]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[8]Department of Biological Sciences, Center for Systems Biology, The University of Texas, Dallas 800 West Campbell Road, RL11, Richardson, TX 75080-3021, USA
Ectopic expression of Oct4, Sox2, Klf4, and c-Myc can reprogram differentiated somatic cells into induced pluripotent stem cells (iPSCs). For years, Oct4 has been considered the key reprogramming factor core of the four factors. Here, we challenge this view by reporting a core function of Sox2 and Klf4 in reprogramming. We found that polycistronic expression of Sox2 and Klf4 was sufficient to induce pluripotency in the absence of exogenous Oct4, and the stoichiometry of Sox2 and Klf4 was essential. Sox2 and Klf4 cooperatively bound across the genome, leading to epigenetic remodeling of their targets, including pluripotency genes and gradual activation of the pluripotency network. Interestingly, cells of different germ layer origins, fibroblasts (mesoderm) and neural progenitor cells (ectoderm), showed convergent reprogramming trajectories and similar efficiency. This work demonstrates a core function of Sox2 and Klf4 in pluripotency induction and shows that this mechanism is independent of germ layer origin.
基金：
Gladstone InstitutesUniversity of California System; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [91519318, 31530025]; National Key R&D Program of China [2017YFA0104000, 2017YFA0104001]
第一作者单位：[1]Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Science, Tsinghua University, Beijing 100084, China
共同第一作者：
通讯作者：
通讯机构：[2]School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China[3]Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA
推荐引用方式(GB/T 7714)：
An Zhaojun,Liu Peng,Zheng Jiashun,et al.Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4[J].CELL REPORTS.2019,29(7):1986-+.doi:10.1016/j.celrep.2019.10.026.
APA：
An, Zhaojun,Liu, Peng,Zheng, Jiashun,Si, Chaozeng,Li, Tianda...&Ding, Sheng.(2019).Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4.CELL REPORTS,29,(7)
MLA：
An, Zhaojun,et al."Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4".CELL REPORTS 29..7(2019):1986-+
生物