4.8 Article

Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2-Jhdm1b-Mkk6-Glis1-Nanog-Essrb-Sall4

期刊

CELL REPORTS
卷 27, 期 12, 页码 3473-+

出版社

CELL PRESS
DOI: 10.1016/j.celrep.2019.05.068

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资金

  1. National Key R&D Program of China [2017YFA0504100, 2016YFA0101800, 2016YFA0100402, 2018YFA0108700, 2016YFA0100801]
  2. Strategic Priority Research Program'' of the Chinese Academy of Sciences [XDA16010204]
  3. Key Research Program of Frontier Sciences of the Chinese Academy of Sciences [QYZDJ-SSW-SMC009]
  4. National Natural Science Foundation of China [31421004, 31530038, 31461143011, 31522033, 31471242, 31550110206]
  5. National Basic Research Program of China [2014CB965200]
  6. Science and Technology Planning Project of Guangdong Province [2015B020228003, 2014B050504008, 2014B020225002, 2014B030301058, 2014B020225006, 2014B05052012]
  7. International Partnership Program of Chinese Academy of Sciences [154144KYSB20160059]
  8. Guangzhou Branch of the Supercomputing Center of the Chinese Academy of Sciences

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Reprogramming somatic cells to pluripotency by Oct4, Sox2, Klf4, and Myc represent a paradigm for cell fate determination. Here, we report a combination of Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb, and Sall4 (7F) that reprogram mouse embryonic fibroblasts or MEFs to chimera competent induced pluripotent stem cells (iPSCs) efficiently. RNA sequencing (RNA-seq) and ATAC-seq reveal distinct mechanisms for 7F induction of pluripotency. Dropout experiments further reveal a highly cooperative process among 7F to dynamically close and open chromatin loci that encode a network of transcription factors to mediate reprogramming. These results establish an alternative paradigm for reprogramming that may be useful for analyzing cell fate control.

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