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2013 Fiscal Year Final Research Report

Identification of master transcription factors in corneal epithelial cells

Research Project

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Project/Area Number 23390404
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KINOSHITA Shigeru  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30116024)

Co-Investigator(Kenkyū-buntansha) UENO Morio  京都府立医科大学, 医学研究科, 助教 (40426531)
KAWASAKI Satoshi  大阪大学, 医学研究科, 講師 (60347458)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords角膜上皮 / 転写因子 / ダイレクトリプログラミング / コア転写因子 / マスターレギュレーター
Research Abstract

We attempted to identify master transcription factors (TFs) in corneal epithelial cells (CECs) which are able to maintain the cell-type specific transcriptional profile. First, we used microarray analysis to select candidate master TFs in CECs from all the genes, which were highly expressed in CECs compared to various other cells. In order to narrow down the master TFs in CECs, iPS interference screening was performed and produced 20 candidate TFs. A particular combination of candidate TFs was able to induce CEC-like cells expressing keratin 12, which is a corneal specific marker when overexpressed in a heterologous cell type. Furthermore, the expression level of other corneal-related genes, such as keratin 3, keratin 15, aldehyde dehydrogenase 3, transketolase, and E-cadherin were upregulated in the induced cells. These results suggested that defined TFs, which enabled the induction of CECs, contributed to the maintenance of the corneal-specific transcriptional profile.

  • Research Products

    (33 results)

All 2014 2013 2012 2011

All Journal Article (13 results) (of which Peer Reviewed: 12 results) Presentation (20 results)

  • [Journal Article] Involvement of cyclin D and p27 in cell proliferation mediated by ROCK inhibitors Y-27632 and Y-39983 during corneal endothelium wound healing2014

    • Author(s)
      Okumura N, Nakano S, Kay EP, Numata R, Ota A, Sowa Y, Sakai T, Ueno M, Kinoshita S, Koizumi N
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 55(1) Pages: 318-29

    • Peer Reviewed
  • [Journal Article] LRIG1 inhibits STAT3-dependent inflammation to maintain corneal homeostasis2014

    • Author(s)
      Nakamura T, Hamuro J, Takaishi M, Simmons S, Maruyama K, Zaffalon A, Bentley AJ, Kawasaki S, Nagata-Takaoka M, Fullwood NJ, Itami S, Sano S, Ishii M, Barrandon Y, Kinoshita S
    • Journal Title

      J Clin Invest

      Volume: 124(1) Pages: 385-397

    • Peer Reviewed
  • [Journal Article] Investigation of gene therapy using immortalized cells derived from a Gelatioous Drop-Like Dystrophy patient2013

    • Author(s)
      Kitazawa K, Kawasaki S, Aoi K, Shinomiya K, Matsuda A, Funaki T, Nakatsukasa M, Murakami A, Kinoshita S
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 54(8) Pages: 5701-11

    • Peer Reviewed
  • [Journal Article] Corneal endothelial cell fate is maintained by LGR5 via the regulation of hedgehog and wnt pathway2013

    • Author(s)
      Hirata-Tominaga K, Nakamura T, Okumura N, Kawasaki S, Kay EP, Barrandon Y, Koizumi N, Kinoshita S
    • Journal Title

      Stem Cells

      Volume: 31(7) Pages: 1396-1407

    • Peer Reviewed
  • [Journal Article] Corneal endothelial expansion promoted by human bone marrow mesenchymal stem cell-derived conditioned medium2013

    • Author(s)
      Nakahara M, Okumura N, Kay EP, Hagiya図3図4 M, Imagawa K, Hosoda Y, Kinoshita S, Koizumi N
    • Journal Title

      PLoS One

      Volume: 8(7) Pages: e69009

    • Peer Reviewed
  • [Journal Article] 角膜の再生医療2013

    • Author(s)
      上野盛夫, 中村隆宏, 木下茂
    • Journal Title

      日本医師会雑誌

      Volume: 142(4) Pages: 777-780

  • [Journal Article] Visual improvement following cultivated oral mucosal epithelial transplantation2013

    • Author(s)
      Sotozono C, Inatomi T, Nakamura T, Koizumi N, Yokoi N, Ueta M, Matsuyama K, Miyakoda K, Kaneda H, Fukushima M, Kinoshita S
    • Journal Title

      Ophthalmology

      Volume: 120(1) Pages: 193-200

    • Peer Reviewed
  • [Journal Article] A novel mutation (p.Glu1389AspfsX16) of the phosphoinositide kinase, FYVE finger containing gene found in a Japanese patient with fleck corneal dystrophy2012

    • Author(s)
      Kawasaki S, Yamasaki K, Nakagawa H, Shinomiya K, Nakatsukasa M, Nakai Y, Kinoshita S
    • Journal Title

      Mol Vis

      Volume: 18 Pages: 2954-60

    • Peer Reviewed
  • [Journal Article] ROCK inhibitor converts corneal endothelial cells into a phenotype capable of regenerating in vivo endothelial tissue2012

    • Author(s)
      Okumura N, Koizumi N, Ueno M, Sakamoto Y, Takahashi H, Tsuchiya H, Hamuro J, Kinoshita S
    • Journal Title

      Am J Pathol

      Volume: 181(7) Pages: 268-277

    • Peer Reviewed
  • [Journal Article] A selective inhibitor of the Rho kinase pathway, Y-27632, and its influence on wound healing in the corneal stroma2012

    • Author(s)
      Yamamoto M, Quantock AJ, Young RD, Okumura N, Ueno M, Sakamoto Y, Kinoshita S, Koizumi N
    • Journal Title

      Mol Vis

      Volume: 18 Pages: 1727-1739

    • Peer Reviewed
  • [Journal Article] Functional role of PPARδ in corneal epithelial wound healing2012

    • Author(s)
      Nakamura Y, Nakamura T, Tarui T, Inoue J, Kinoshita S
    • Journal Title

      Am J Pathol

      Volume: 180(2) Pages: 583-598

    • Peer Reviewed
  • [Journal Article] Enhancement of corneal endothelium wound healing by a ROCK inhibitor eye drop2011

    • Author(s)
      Okumura N, Koizumi N, Ueno M, Sakamoto Y, Takahashi H, Hirata K, Torii R, Hamuro J, Kinoshita S
    • Journal Title

      Br J Ophthalmol

      Volume: 95(7) Pages: 1006-1009

    • Peer Reviewed
  • [Journal Article] Long-term results of autologous cultivated oralmucosal epithelial transplantation in the scar phase of severe ocular surface disorders2011

    • Author(s)
      Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S
    • Journal Title

      Br J Ophthalmol

      Volume: 95(7) Pages: 942-946

    • Peer Reviewed
  • [Presentation] Investigation of Gene Therapy and Pathophysiology Using Immortalized Cells Derived from a Gelatinous Drop-Like Dystrophy Patient2014

    • Author(s)
      Kitazawa K, Kawasaki S, Aoi K, Shinomiya K, Matsuda A, Funaki T, Nakatsukasa M, Murakami A, Kinoshita S
    • Organizer
      Gordon Research Seminar
    • Place of Presentation
      Ventura, USA
    • Year and Date
      2014-02-16
  • [Presentation] LRIG1 による角膜の恒常性維持機構の解析2014

    • Author(s)
      中村隆宏, 羽室淳爾, 高石樹朗, 丸山和一, 永田真帆, 川崎論, 板見智, 佐野栄紀, 石井優, 木下茂
    • Organizer
      角膜カンファランス2014
    • Place of Presentation
      沖縄
    • Year and Date
      2014-01-31
  • [Presentation] 角膜上皮細胞におけるR-spondin1 の機能解析2014

    • Author(s)
      大倉翔貴, 中村隆宏, 畑友衣子, 小林正和, 永田真帆, 小泉範子, 木下茂
    • Organizer
      角膜カンファランス2014
    • Place of Presentation
      沖縄
    • Year and Date
      2014-01-31
  • [Presentation] 眼表面扁平上皮腫瘍におけるLRIG1発現解析2014

    • Author(s)
      永田真帆, 中村隆宏, 外園千恵, 稲富勉, 横井則彦, 木下茂
    • Organizer
      角膜カンファランス2014
    • Place of Presentation
      沖縄
    • Year and Date
      2014-01-31
  • [Presentation] ヒト角膜上皮細胞シートの安定的な製造を可能にするシート作製技術の開発2014

    • Author(s)
      前田謙一, 横山修一, 細田勇喜, 渡部俊介, 今川究, 中村隆宏, 木下茂
    • Organizer
      角膜カンファランス2014
    • Place of Presentation
      沖縄
    • Year and Date
      2014-01-30
  • [Presentation] Investigation of gene therapy using immortalized cells derived from a Gelatioous Drop-Like Dystrophy patient2013

    • Author(s)
      Kitazawa K, Kawasaki S, Aoi K, Shinomiya K, Matsuda A, Funaki T, Nakatsukasa M, Murakami A, Kinoshita S
    • Organizer
      The Association for Research in Vision and Ophthalmology, Seatle (ARVO) 2013
    • Place of Presentation
      Seatle, USA
    • Year and Date
      2013-05-08
  • [Presentation] Integral Analysis of Gene Signatures and MicroRNA Expression of Cultured Human Corneal Endothelial Cells in Relation to Their Functions, Cell Senescence, Epithelial-Mesenchymal Transition, and Fibrosis2013

    • Author(s)
      Asada K, Toda M, Hagiya M, Nakata K, Ueno M, Okumura N, Koizumi N, Hamuro J, Kinoshita S
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2013-05-07
  • [Presentation] Transfer of TACSTD2 gene into corneal epithelial cells of Gelatinous drop like corneal dystrophy and its functional expression2013

    • Author(s)
      Matsunaga T, Kitazawa K, Yamasaki K, Sato T, Watanabe Y, Funaki T, Matsuda A, Ebihara N, Kawasaki S, Murakami A
    • Organizer
      The Association for Research in Vision and Ophthalmology, Seatle (ARVO) 2013
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2013-05-07
  • [Presentation] Efficacy and Safety Evaluation of Cell-Injection Therapy using Cultivated Human Corneal Endothelial Cells2013

    • Author(s)
      Koizumi N, Okumura N, Shiina T, Suzuki S, Nakamura S, Sakamoto Y, Yamasaki K, Ueno M, Hamuro J, Kinoshita S
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2013-05-06
  • [Presentation] Rho kinase inhibitor promotes cell adhesion of corneal endothelial cells through inhibiting phosphorylation of MLC2013

    • Author(s)
      Tsujimoto Y, Okumura N, Kay EP, Numata R, Kinoshita S, Koizumi N
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2013-05-06
  • [Presentation] A new method for the efficient and less-stress dissociation of corneal epithelial cells2013

    • Author(s)
      Shinomiya K, Kawasahi S, Aoi K, Kitazawa K, Kinoshita S
    • Organizer
      The Association for Research in Vision and Ophthalmology, Seatle (ARVO) 2013
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2013-05-05
  • [Presentation] 羊膜を基質とし作成した口腔粘膜再生シートを用いた尿路再建2012

    • Author(s)
      内藤泰行, 河内明宏, 邵仁晢, 中村隆宏, 稲富勉, 木下茂, 美紀恒治
    • Organizer
      第11回日本再生医療学会
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-12
  • [Presentation] Establishment of immortalized corneal and conjunctival epithelial cells lacking the functional TACSTD2 gene2012

    • Author(s)
      Kitazawa K, Kawasaki S, Shinomiya K, Matsuda A, Funaki F, Yamasaki K, Nakatsukasa M, Fukuoka H, Ebihara N, Murakami A, Kinoshita S
    • Organizer
      The Association for Research in Vision and Ophthalmology, Fort Lauderdale (ARVO) 2012
    • Place of Presentation
      Ft. Lauderdale, USA
    • Year and Date
      2012-05-07
  • [Presentation] 結膜腫瘍でのLeucine-rich repeats and immunoglobulin-like domains 1(LRIG1)の発現2012

    • Author(s)
      永田真帆, 中村隆宏, 外園千恵, 稲富勉, 横井則彦, 板見智, 木下茂
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-05
  • [Presentation] 角膜上皮化生をきたした培養口腔粘膜上皮移植の1 例2012

    • Author(s)
      張佑子, 外園千恵, 中川絋子, 中村隆宏, 稲富勉, 上田真由美, 横井則彦, 木下茂
    • Organizer
      角膜カンファランス2012
    • Place of Presentation
      東京
    • Year and Date
      2012-02-23
  • [Presentation] 角膜扁平上皮癌におけるGPR49 の発現の検討2012

    • Author(s)
      平田香菜, 中村隆宏, 外園千恵, 稲富勉, 奥村直毅, 小泉範子, 横井則彦, 木下茂
    • Organizer
      角膜カンファランス2012
    • Place of Presentation
      東京
    • Year and Date
      2012-02-23
  • [Presentation] 全層角膜移植の11 年間の動向と治療成績2012

    • Author(s)
      堀内稔子, 中川絋子, 稲富勉, 上田真由美, 中村隆宏, 小泉範子, 外園千恵, 横井則彦, 木下茂
    • Organizer
      角膜カンファランス2012
    • Place of Presentation
      東京
    • Year and Date
      2012-02-23
  • [Presentation] Cultivated Oral Mucosal Epithelial Transplantation for Ocular Surface Reconstruction in Stevens-Johnson Syndrome2011

    • Author(s)
      Sotozono C, Inatomi T, Nakamura T, Ueta M, Yokoi N, Miyakoda K, Kinoshita S
    • Organizer
      第115回米国眼科学会議(AAO)
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-10-24
  • [Presentation] 難治性角結膜疾患に対する自家培養口腔粘膜上皮シート移植のレトロスペクティブ調査2011

    • Author(s)
      外園千恵, 稲富勉, 中村隆宏, 小泉範子, 横井則彦, 都田桂子 , 松山琴音, 木下茂
    • Organizer
      第65回日本臨床眼科学会
    • Place of Presentation
      東京
    • Year and Date
      2011-10-08
  • [Presentation] 自家培養口腔粘膜上皮シート移植による結膜嚢再建効果の検討2011

    • Author(s)
      稲富勉, 外園千恵, 中村隆宏, 小泉範子, 都田桂子, 松山琴音, 木下茂
    • Organizer
      第65回日本臨床眼科学会
    • Place of Presentation
      東京
    • Year and Date
      2011-10-08

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Published: 2015-06-25  

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