BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone

被引:104
作者
Chen, Jiekai [1 ]
Liu, Jing [1 ]
Yang, Jiaqi [1 ]
Chen, You [1 ]
Chen, Jing [1 ]
Ni, Su [1 ]
Song, Hong [1 ]
Zeng, Lingwen [1 ]
Ding, Ke [1 ]
Pei, Duanqing [1 ]
机构
[1] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, S China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Oct4; iPSCs; reprogramming; stem cell; BMPs; MET; PLURIPOTENT STEM-CELLS; GENERATION; INDUCTION; MYC;
D O I
10.1038/cr.2010.172
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Generation of induced pluripotent stem cells by defined factors has become a useful model to investigate the mechanism of reprogramming and cell fate determination. However, the precise mechanism of factor-based reprogramming remains unclear. Here, we show that Klf4 mainly acts at the initial phase of reprogramming to initiate mesenchymal-to-epithelial transition and can be functionally replaced by bone morphogenetic proteins (BMPs). BMPs boosted the efficiency of Oct4/Sox2-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to similar to 1%. BMPs also promoted single-factor Oct4-based reprogramming of MEFs and tail tibial fibroblasts. Our studies clarify the contribution of Klf4 in reprogramming and establish Oct4 as a singular setter of pluripotency in differentiated cells.
引用
收藏
页码:205 / 212
页数:8
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