BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone.
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 ∼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.
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine at Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Jiekai
J
Chen
Jing
J
Liu
Jiaqi
J
Yang
You
Y
Chen
Jing
J
Chen
Su
S
Ni
Hong
H
Song
Lingwen
L
Zeng
Ke
K
Ding
Duanqing
D
Pei
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000502:physiology; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism* / Q000502:physiology; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016256:Lewis X Antigen; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C513672:Zfp42 protein, mouse; D014157:Transcription Factors