CAS Key Laboratory of Regenerative Biology, South China Institutes for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
CAS Key Laboratory of Regenerative Biology, South China Institutes for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Cell Rep. 2019 Jun 18;27(12):3473-3485.e5. doi: 10.1016/j.celrep.2019.05.068.
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.
通过 Oct4、Sox2、Klf4 和 Myc 将体细胞重编程为多能性代表了细胞命运决定的范例。在这里,我们报告了 Jdp2、Jhdm1b、Mkk6、Glis1、Nanog、Essrb 和 Sall4(7F)的组合,可有效地将小鼠胚胎成纤维细胞或 MEFs 重编程为嵌合能力的诱导多能干细胞(iPSCs)。RNA 测序(RNA-seq)和 ATAC-seq 揭示了 7F 诱导多能性的不同机制。dropout 实验进一步揭示了 7F 之间在动态关闭和打开编码转录因子网络以介导重编程的染色质基因座的高度协作过程。这些结果建立了一种可用于分析细胞命运控制的替代重编程范例。