Reprogramming of mouse cochlear cells by transcription factors to generate induced pluripotent stem cells.
As an initial step for using technology derived from induced pluripotent stem cells (iPSCs) in the field of inner ear therapeutics, we examined the potential of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, which are employed in the generation of iPSCs, for dedifferentiating cochlear epithelial cells. Otospheres, which are sphere-forming cells derived from dissociated cochlear epithelial cells of neonatal mice, were used as a cell source. The four transcription factors were introduced into otospheres using retroviral vectors. Virally transduced otospheres formed embryonic stem cell-like colonies that expressed markers for pluripotent stem cells and were capable of differentiating into the three germ layers in vivo and in vitro. These findings illustrate that viral transduction of four transcription factors can lead to reprogramming of cochlear epithelial cells, which may contribute to future studies of dedifferentiation of cochlear epithelial cells in tissue and identification of key molecules for otic induction.
1 Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University , Kyoto, Japan , 6068507.
Xiang-Xin
XX
Lou
Takayuki
T
Nakagawa
Koji
K
Nishimura
Hiroe
H
Ohnishi
Norio
N
Yamamoto
Tatsunori
T
Sakamoto
Juichi
J
Ito
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D003051:Cochlea / Q000166:cytology*; D017931:DNA Primers; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*; D014161:Transduction, Genetic
D017931:DNA Primers; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors