title: OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition.
abstract: 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.
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan; Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan; Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan; CREST (Core Research for Evolutional Science and Technology), JST (Japan Science and Technology Agency), Honcho 4-1-8 Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kitazawa
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Takafusa
authors.initials: T
authors.lastname: Hikichi
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan; Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Mitsunaga
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamakawa
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Furukawa
authors.affiliation: JBIC Research Institute, Japan Biological Informatics Consortium, TIME24 Building 10F 2-4-32 Aomi Koto-ku, Tokyo 135-8073, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Takasaka
authors.affiliation: 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.
authors.forename: Naoki
authors.initials: N
authors.lastname: Goshima
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan; Department of Ophthalmology, Osaka University, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawasaki
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan; Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Hirokoji-agaru Kawaramachi-dori Kamigyo-ku, Kyoto 602-0841, Japan. Electronic address: shigeruk@koto.kpu-m.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho Shogoin Sakyo-ku, Kyoto 606-8507, Japan; CREST (Core Research for Evolutional Science and Technology), JST (Japan Science and Technology Agency), Honcho 4-1-8 Kawaguchi, Saitama 332-0012, Japan. Electronic address: smasui@cira.kyoto-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Masui
mesh_terms: D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D019573:Epithelium, Corneal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C544941:Ovol2 protein, human; D014157:Transcription Factors