Induction of pluripotent stem cells from human third molar mesenchymal stromal cells.
The expression of four transcription factors (OCT3/4, SOX2, KLF4, and MYC) can reprogram mouse as well as human somatic cells to induced pluripotent stem (iPS) cells. We generated iPS cells from mesenchymal stromal cells (MSCs) derived from human third molars (wisdom teeth) by retroviral transduction of OCT3/4, SOX2, and KLF4 without MYC, which is considered as oncogene. Interestingly, some of the clonally expanded MSCs could be used for iPS cell generation with 30-100-fold higher efficiency when compared with that of other clonally expanded MSCs and human dermal fibroblasts. Global gene expression profiles demonstrated some up-regulated genes regarding DNA repair/histone conformational change in the efficient clones, suggesting that the processes of chromatin remodeling have important roles in the cascade of iPS cells generation. The generated iPS cells resembled human embryonic stem (ES) cells in many aspects, including morphology, ES marker expression, global gene expression, epigenetic states, and the ability to differentiate into the three germ layers in vitro and in vivo. Because human third molars are discarded as clinical waste, our data indicate that clonally expanded MSCs derived from human third molars are a valuable cell source for the generation of iPS cells.
Oda
Yasuaki
Y
Tissue Engineering Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology, Hyogo 661-0974, Japan.
Yoshimura
Yasuhide
Y
Ohnishi
Hiroe
H
Tadokoro
Mika
M
Katsube
Yoshihiro
Y
Sasao
Mari
M
Kubo
Yoko
Y
Hattori
Koji
K
Saito
Shigeru
S
Horimoto
Katsuhisa
K
Yuba
Shunsuke
S
Ohgushi
Hajime
H
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007621:Karyotyping; D000090062:Kruppel-Like Factor 4; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D014070:Tooth / Q000166:cytology*