OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition
Koji Kitazawa,
Takafusa Hikichi,
Takahiro Nakamura,
Kanae Mitsunaga,
Azusa Tanaka,
Masahiro Nakamura,
Tatsuya Yamakawa,
Shiori Furukawa,
Mieko Takasaka,
Naoki Goshima,
Akira Watanabe,
Keisuke Okita,
Satoshi Kawasaki,
Morio Ueno,
Shigeru Kinoshita,
Shinji Masui
Affiliations
Koji Kitazawa
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Takafusa Hikichi
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Takahiro Nakamura
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan
Kanae Mitsunaga
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Azusa Tanaka
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Masahiro Nakamura
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Tatsuya Yamakawa
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Shiori Furukawa
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Mieko Takasaka
JBIC Research Institute, Japan Biological Informatics Consortium, TIME24 Building 10F 2-4-32 Aomi Koto-ku, Tokyo 135-8073, Japan
Naoki Goshima
Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Waterfront Bio-IT Research Building, 2-4-7 Aomi Koto-ku, Tokyo 135-0064, Japan
Akira Watanabe
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Keisuke Okita
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Satoshi Kawasaki
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan
Morio Ueno
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan
Shigeru Kinoshita
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan
Shinji Masui
Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan
In development, embryonic ectoderm differentiates into neuroectoderm and surface ectoderm using poorly understood mechanisms. Here, we show that the transcription factor OVOL2 maintains the transcriptional program of human corneal epithelium cells (CECs), a derivative of the surface ectoderm, and that OVOL2 may regulate the differential transcriptional programs of the two lineages. A functional screen identified OVOL2 as a repressor of mesenchymal genes to maintain CECs. Transduction of OVOL2 with several other transcription factors induced the transcriptional program of CECs in fibroblasts. Moreover, neuroectoderm derivatives were found to express mesenchymal genes, and OVOL2 alone could induce the transcriptional program of CECs in neural progenitors by repressing these genes while activating epithelial genes. Our data suggest that the difference between the transcriptional programs of some neuroectoderm- and surface ectoderm-derivative cells may be regulated in part by a reciprocally repressive mechanism between epithelial and mesenchymal genes, as seen in epithelial-to-mesenchymal transition.
