Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2.
Induced pluripotent stem cell technology has attracted enormous interest for potential application in regenerative medicine. Here, we report that a specific glycogen synthase kinase 3 (GSK-3) inhibitor, CHIR99021, can induce the reprogramming of mouse embryonic fibroblasts transduced by only two factors, Oct4 and Klf4. When combined with Parnate (also named tranylcypromine), an inhibitor of lysine-specific demethylase 1, CHIR99021 can cause the reprogramming of human primary keratinocyte transduced with the two factors, Oct4 and Klf4. To our knowledge, this is the first time that human iPS cells have been generated from somatic cells without exogenous Sox2 expression. Our studies suggest that the GSK-3 inhibitor might have a general application to replace transcription factors in both mouse and human reprogramming.
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
Wenlin
W
Li
HongYan
H
Zhou
Ramzey
R
Abujarour
Saiyong
S
Zhu
Jin
J
Young Joo
Tongxiang
T
Lin
Ergeng
E
Hao
Hans R
HR
Schöler
Alberto
A
Hayek
Sheng
S
Ding
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*
C473711:Chir 99021; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D038362:Glycogen Synthase Kinase 3