Generation of induced pluripotent stem cells from human adipose-derived stem cells without c-MYC.
Human adipose-derived stem cells (hASCs) are ubiquitous, plentiful, and easily/safely obtainable cells derived from adipose tissue, regardless of the age and sex of the donor. However, the hASCs have limited proliferative and differentiation capabilities. In this study, we examined whether induced pluripotent stem cells (iPSCs) could be generated from hASCs. We transduced hASCs with three human transcription factors (OCT3/4, SOX2, and KLF4), and found that they formed human embryonic stem cell (ESC)-like colonies. Importantly, we did not transduce c-MYC, which is usually utilized to generate iPSCs but is considered an oncogene. These colonies expressed human ESC-specific surface antigens (stage-specific embryonic antigens SSEA-3 and SSEA-4, and tumor-related antigens TRA-1-60 and TRA-1-81), endogenous transcription factors (OCT3/4, NANOG, and SOX2), and undifferentiated human ESC marker genes (REX1, UTF1, GDF3, DPPA2, DPPA4, and DPPA5). Further, the colonies were able to differentiate into the three germ layers both in vitro and in vivo. These results show that human iPSCs can be generated by the transduction of three factors (OCT3/4, SOX2, and KLF4) into hASCs.
Tissue Engineering Research Group, Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, Amagasaki, Hyogo, Japan.
Tetsuhiro
T
Aoki
Hiroe
H
Ohnishi
Yasuaki
Y
Oda
Mika
M
Tadokoro
Mari
M
Sasao
Hiroyuki
H
Kato
Koji
K
Hattori
Hajime
H
Ohgushi
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007621:Karyotyping; D000090062:Kruppel-Like Factor 4; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013724:Teratoma / Q000473:pathology
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D016271:Proto-Oncogene Proteins c-myc