Notch signaling regulates the homeostatic function of corneal epithelial stem cells.

• Project/Area Number: 21791721
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Doshisha University
• Principal Investigator: NAKAMURA Takahiro Doshisha University, 生命医科学部, 准教授 (30411078)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 眼発生 / 再生医学 / 上皮幹細胞 / 角膜 / Notchシグナル / Hes1 / 眼表面

Research Abstract

Hes1, a major target gene in Notch signaling, is essential for corneal and eye morphogenesis. Hes1 is mainly expressed in the corneal epithelial stem/progenitor cells and is not detected in the differentiated corneal epithelial cells. Forced Hes1 expression inhibits the differentiation of corneal epithelial stem/progenitor cells and maintains these cells' undifferentiated state. Our data provides the first evidence that Hes1 is essential for corneal morphogenesis and regulates the homeostatic function of corneal epithelial stem/progenitor cells.

Research Products

• [Journal Article] Micro spectroscopy of spectral biomarkers associated with human corneal stem cells. (2010)
  • Author(s): Nakamura T, Kelly JG, Trevisan J, Cooper LJ, Carmichael PL, Scott AC, Cotte M, Susini J, Martin-Hirsch PL, Kinoshita S, Fullwood NJ, Martin F
  • Journal Title: Mol Vis. 16 Pages: 359-368
  • Peer Reviewed
• [Journal Article] The variation in transparency of amniotic membrane used in ocular surface regeneration. (2010)
  • Author(s): Connon CJ, Doutch J, Chen B, Hopkinson A, Mehta JS, Nakamura T, Kinoshita S, Meek KM
  • Journal Title: Br J Ophthalmol. 94(8) Pages: 963-964
  • Peer Reviewed
• [Journal Article] Evidence for a stem-cell lineage in corneal squamous cell carcinoma using synchrotronbased Fourier- transform infrared microspectroscopy and multivariate analysis. (2010)
  • Author(s): Kelly JG, Nakamura T, Kinoshita S, Fullwood NJ, Martin FL
  • Journal Title: Analyst. 135(12) Pages: 3120-3125
  • Peer Reviewed
• [Journal Article] Long-Term Phenotypic Study After Allogeneic Cultivated Corneal Limbal Epithelial Transplantation for Severe Ocular Surface Diseases. (2010)
  • Author(s): Nakamura T, Sotozono C, Bentley AJ, Mano S, Inatomi T, Koizumi N, Fullwood NJ, Kinoshita S
  • Journal Title: Ophthalmology. 117(12) Pages: 2247-2254
  • Peer Reviewed
• [Journal Article] Micro spectroscopy of spectral biomarkers associated with human corneal stem cells. (2010)
  • Author(s): Nakamura T
  • Journal Title: Molecular Vision Volume: 16巻 Pages: 359-368
  • Peer Reviewed
• [Journal Article] The variation in transparency of amniotic membrane used in ocular surface regeneration. (2010)
  • Author(s): Connon CJ
  • Journal Title: British Journal of Ophthalmology Volume: 94巻 Pages: 963-964
  • Peer Reviewed
• [Journal Article] Evidence for a stem-cell lineage in corneal squamous cell carcinoma using synchrotronbased Fourier-transform infrared microspectroscopy and multivariate analysis. (2010)
  • Author(s): 3Kelly JG
  • Journal Title: Analyst Volume: 135巻 Pages: 3120-3125
  • Peer Reviewed
• [Journal Article] Long-Term Phenotypic Study After Allogeneic Cultivated Corneal Limbal Epithelial Transplantation for Severe Ocular Surface Diseases. (2010)
  • Author(s): Nakamura T
  • Journal Title: Ophthalmology Volume: 117巻 Pages: 2247-2254
  • Peer Reviewed
• [Journal Article] Discrimination of human stem cells by photothermal microspectroscopy. (2009)
  • Author(s): Grude O, Nakamura T, Hammiche A, Bentley AJ, Martin FL, Pollock HM, Kinoshita S, Fullwood NJ.
  • Journal Title: Vibrational Spectroscopy. 49(1) Pages: 22-27
  • Peer Reviewed
• [Journal Article] Characteristic morphology and distribution of bone marrow derived cells in the cornea. (2009)
  • Author(s): Takayama T, Kondo T, Kobayashi M, Ohta K, Ishibashi Y, Kanemaru T, Shimazu H, Ishikawa F, Nakamura T, Kinoshita S, Nakamura K
  • Journal Title: The Anatomical Record. 292(5) Pages: 756-763
  • Peer Reviewed
• [Journal Article] Novel Sutureless Keratoplasty with a Chemically Defined Bioadhesive. (2009)
  • Author(s): Takaoka M, Nakamura T, Sugai H, Bentley AJ, Nakajima N, Yokoi N, Fullwood NJ, Hyon SH, Kinoshita S
  • Journal Title: Invest Ophthalmol Vis Sci. 50(6) Pages: 2679-2685
  • Peer Reviewed
• [Journal Article] Discrimination of human stem cells by photothermal microspectroscopy (2009)
  • Author(s): Grude O, Nakamura T, et al.
  • Journal Title: Vibrational Spectroscopy 49 Pages: 22-27
  • Peer Reviewed
• [Journal Article] Characteristic morphology and distribution of bone marrow derived cells in the cornea (2009)
  • Author(s): Takayama T, Nakamura T, et al.
  • Journal Title: The Anatomical Record 292 Pages: 756-763
  • Peer Reviewed
• [Journal Article] Novel Sutureless Keratoplasty with a Chemically Defined Bioadhesive (2009)
  • Author(s): Takaoka M, Nakamura T, et al.
  • Journal Title: Investigative Ophthalmology & Visual Science 50 Pages: 2679-2685
  • Peer Reviewed
• [Journal Article] 角膜 (2009)
  • Author(s): 中村隆宏, 木下茂
  • Journal Title: 遺伝子医学MOOK 13号 Pages: 295-298
• [Presentation] 重症眼表面疾患に対する眼表面再建術と輪部支持型ハードコンタクトレンズ装用 (2011)
  • Author(s): 外園千恵
  • Organizer: 角膜カンファランス2011 (第35回日本角膜学会総会 第27回日本角膜移植学会)
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2011-02-18
• [Presentation] 間接リウマチによる難治性強膜炎に非典型的な角膜上皮障害を合併した1例 (2011)
  • Author(s): 畑匡侑
  • Organizer: 角膜カンファランス2011 (第35回日本角膜学会総会第27回日本角膜移植学会)
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2011-02-17
• [Presentation] 局所麻酔点眼中毒による両眼性遷延性上皮欠損の一例 (2011)
  • Author(s): 熊谷京子
  • Organizer: 角膜カンファランス2011 (第35回日本角膜学会総会第27回日本角膜移植学会)
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2011-02-17
• [Presentation] 難治性眼表面疾患に対する自己培養口腔粘膜上皮移植術と眼瞼手術同時併用治療の検討 (2011)
  • Author(s): 竹田一徳
  • Organizer: 角膜カンファランス2011 (第35回日本角膜学会総会 第27回日本角膜移植学会)
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2011-02-17
• [Presentation] Long-Term Clinical Results of Autologous Cultivated Corneal Limbal Epithelial Transplantation in Severe Ocular Surface Disease. (2010)
  • Author(s): Nakamura T
  • Organizer: The 2nd Asia Cornea Society Biennial Scientific Meeting
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-12-03
• [Presentation] Long-Term Results of Autologous Cultivated Oral Mucosal Epithelial Transplantation in The Scar Phase of Severe Ocular Surface Disease. (2010)
  • Author(s): Nakamura T
  • Organizer: 2010 Korea-Kyoto Joint Cornea Conference
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-12-03
• [Presentation] Long-Term Clinical Results of Autologous Cultivated Corneal Limbal Epithelial Transplantation in Severe Ocular Surface Disease. (2010)
  • Author(s): Nakamura T
  • Organizer: The 2nd Asia Cornea Society Biennial Scientific Meeting
  • Place of Presentation: The Westin Miyako Hotel, Kyoto (Kyoto)
  • Year and Date: 2010-12-03
• [Presentation] Long-Term Results of Autologous Cultivated Oral Mucosal Epithelial Transplantation in The Scar Phase of Severe Ocular Surface Disease. (2010)
  • Author(s): Nakamura T
  • Organizer: 2010 Korea-Kyoto Joint Cornea Conference
  • Place of Presentation: The Westin Miyako Hotel, Kyoto (Kyoto)
  • Year and Date: 2010-12-03
• [Presentation] 無水晶体眼水疱性角膜症に対する角膜内皮移植術の応用と術式選択 (2010)
  • Author(s): 稲富勉
  • Organizer: 第64回日本臨床眼科学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2010-11-12
• [Presentation] GMP準拠細胞培養施設による培養上皮移植の臨床成績 (2010)
  • Author(s): 中村隆宏
  • Organizer: 第64回日本臨床眼科学会
  • Place of Presentation: 神戸国際会議場(神戸)
  • Year and Date: 2010-11-12
• [Presentation] Hes1 Regulates Corneal Development and The Function of Corneal Epithelial Stem Progenitor Cells. (2010)
  • Author(s): Nakamura T, KinoshitaS
  • Organizer: XIX Biennial Meeting of the International Society for Eye Research(ISER)
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2010-07-22
• [Presentation] Hesl Regulates Corneal Development and The Function of Corneal Epithelial Stem Progenitor Cells. (2010)
  • Author(s): Nakamura T
  • Organizer: XIX Biennial Meeting of the International Society for Eye Research
  • Place of Presentation: Hilton Montreal Bonaventure (Montreal)
  • Year and Date: 2010-07-22
• [Presentation] 再生医療で光を～角膜再生への挑戦 (2010)
  • Author(s): 中村隆宏
  • Organizer: 第9回国際バイオEXPOバイオアカデミックフォーラム
  • Place of Presentation: 東京ビッグサイト(東京)
  • Year and Date: 2010-07-01
• [Presentation] Podoplanin Regulates Corneal Epithelial Morphology. (2010)
  • Author(s): Maruyama K, Bock F, Schlotzer-Schrehardt U, Nakamura T, Kerjaschki D, Kruse F.E, Kinoshita S, Cursiefen C
  • Organizer: 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2010-05-06
• [Presentation] Podoplanin Regulates Corneal Epithelial Morphology. (2010)
  • Author(s): Maruyama K
  • Organizer: 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Greater Fort Lauderdale Broward County Convention Center (Florida)
  • Year and Date: 2010-05-06
• [Presentation] Long-Term Results of Autologous Cultivated Corneal Limbal Epithelial Transplantation in Severe Ocular Surface Disorders. (2010)
  • Author(s): Nakamura T, Inatomi T, Sotozono C, Koizumi N, Kinoshita S
  • Organizer: 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2010-05-02
• [Presentation] Long-Term Results of Autologous Cultivated Corneal Limbal Epithelial Transplantation in Severe Ocular Surface Disorders. (2010)
  • Author(s): Nakamura T
  • Organizer: 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Greater Fort Lauderdale Broward County Convention Center (Florida)
  • Year and Date: 2010-05-02
• [Presentation] 培養粘膜上皮の細胞増殖に対するBevacizumabの作用 (2010)
  • Author(s): 丸山和一
  • Organizer: 第114回日本眼科学会総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2010-04-16
• [Presentation] Autologous Cultivated Oral Mucosal Epithelial Teansp;antation in Severe Ocular Surface Disorders : Long-Term Results. (2010)
  • Author(s): Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S
  • Organizer: World Cornea Congress VI
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-04-09
• [Presentation] Autologous Cultivated Oral Mucosal Epithelial Teansp ; antation in Severe Ocular Surface Disorders : Long-Term Results. (2010)
  • Author(s): Nakamura T
  • Organizer: World Cornea Congress VI
  • Place of Presentation: Boston Convention & Exhibition Center (Boston)
  • Year and Date: 2010-04-09
• [Presentation] New development of corneal epithelial regeneration. (2009)
  • Author(s): Nakamura T
  • Organizer: 3rd KPUM-FAU Erlangen-Nurnberg Joint Meeting. Erlangen
  • Place of Presentation: Germany
  • Year and Date: 2009-11-10
• [Presentation] New development of corneal epithelia regeneration (2009)
  • Author(s): 中村隆宏
  • Organizer: 3rd KPUM-FAU Erlangen-Numberg Joint Meeting
  • Place of Presentation: Erlangen, Germany
  • Year and Date: 2009-11-10
• [Presentation] 角膜再生医療の新たな展開 (2009)
  • Author(s): 中村隆宏
  • Organizer: 京都府立医科大学「研究開発センター」第11回学術講演会(JST戦略的国際科学技術推進事業 日本-スイス研究交流事業)
  • Place of Presentation: 京都府立医科大学(京都)
  • Year and Date: 2009-11-04
• [Presentation] 難治性眼表面疾患に対する自己培養角膜上皮移植術の長期臨床成績 (2009)
  • Author(s): 中村隆宏, 他
  • Organizer: 第63回日本臨床眼科学会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2009-10-11
• [Presentation] Long-Term Results of Autologous Cultivated Oral Mucosal Epithelial Transplantation in Severe Ocular Surface Disorders. (2009)
  • Author(s): Nakamura T, K Takeda, T Inatomi, C Sotozono, S Kinoshita
  • Organizer: 2009 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2009-05-07
• [Presentation] Phenotypic Analysis of Cultivated Oral Mucosal Epithelium Transplanted on a Human Cornea. (2009)
  • Author(s): Inatomi T, Nakamura T, Koizumi N, Sotozono C, Kinoshita S
  • Organizer: 2009 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2009-05-07
• [Presentation] Long-Term Results of Autologous Cultivated Oral Mucosal Epithelial Transplantation in Severe Ocular Surface Disorders (2009)
  • Author(s): 中村隆宏 et al.
  • Organizer: 2009 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2009-05-07
• [Presentation] Phenotypic Analysis of Cultivated Oral Mucosal Epithelium Transplanted on a Human Cornea (2009)
  • Author(s): Inatomi T, Nakamura T et al.
  • Organizer: 2009 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2009-05-07
• [Presentation] Multicenter Prospective Analysis of Cultured Corneal Epithelial Sheet Transplantation. (2009)
  • Author(s): Sotozono C, Nakamura T, Inatomi T, Hamuro J, Satake Y, Shimazaki J, Tsubota K, Hara Y, Ohashi Y, Kinoshita S
  • Organizer: 2009 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2009-05-04
• [Presentation] Multicenter Prospective Analysis of Cultured Corneal Epithelial Sheet Transplantation (2009)
  • Author(s): Sotozono C, Nakamura T et al.
  • Organizer: 2009 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, Florida, USA
  • Year and Date: 2009-05-04
• [Presentation] GMP準拠細胞プロセシング施設を用いた難治性眼表面疾患に対する培養口腔粘膜上皮移植術の試み (2009)
  • Author(s): 中村隆宏, 他
  • Organizer: 第8回日本再生医療学会総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2009-03-05
• [Presentation] 羊膜移植の適応と効果 (2009)
  • Author(s): 日野智之, 中村隆宏, 他
  • Organizer: 第33回角膜カンファランス 第25回日本角膜移植学会
  • Place of Presentation: ザ・リッツ・カールトン大阪
  • Year and Date: 2009-02-20
• [Presentation] 重篤な肺合併症を伴う Stevens-Johnson 症候群に対する自己培養口腔粘膜上皮シート移植 (2009)
  • Author(s): 熊谷京子, 中村隆宏, 他
  • Organizer: 第33回角膜カンファランス 第25回日本角膜移植学会
  • Place of Presentation: ザ・リッツ・カールトン大阪
  • Year and Date: 2009-02-20
• [Presentation] 難治性眼表面疾患に対する自己培養口腔粘膜上皮移植術の長期臨床成績 (2009)
  • Author(s): 竹田一徳, 中村隆宏, 他
  • Organizer: 第33回角膜カンファランス 第25回日本角膜移植学会
  • Place of Presentation: ザ・リッツ・カールトン大阪
  • Year and Date: 2009-02-19
• [Presentation] 食品添加物由来の生体接着剤を用いた無縫合角膜移植手術の開発 (2009)
  • Author(s): 高岡真帆, 中村隆宏, 他
  • Organizer: 第33回角膜カンファランス 第25回日本角膜移植学会
  • Place of Presentation: ザ・リッツ・カールトン大阪
  • Year and Date: 2009-02-19
• [Book] 角膜疾患 難治性眼表面疾患の克服に向けて.臨床眼科 64(13) (2010)
  • Author(s): 中村隆宏
• [Book] 臨床眼科 特集 基礎研究から難治性眼疾患のブレークスルーをねらえ角膜疾患 難治性眼表面疾患の克服に向けて (2010)
  • Author(s): 中村隆宏
  • Total Pages: 110
  • Publisher: 医学書院
• [Book] 角膜.遺伝子医学MOOK13号 (2009)
  • Author(s): 中村隆宏, 木下茂
• [Book] 角膜の再生医療.綜合臨床, 58(1) (2009)
  • Author(s): 中村隆宏, 木下茂