Elucidation of molecular mechanism of corneal epithelial stem cells using lineage tracing analysis

• Project/Area Number: 26462702
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyoto Prefectural University of Medicine (2015-2016); Doshisha University (2014)
• Principal Investigator: NAKAMURA TAKAHIRO 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (30411078)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 角膜上皮 / 上皮幹細胞 / 細胞系譜解析 / Lrig1 / 創傷治癒

Outline of Final Research Achievements

In order to investigate the mechanism of the homeostatic maintenance of corneal epithelial stem cells, we successfully generated leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) knock-in mice. Using those mice, we found that LRIG1(+) corneal epithelial stem cells are not only located in the limbal region, but also in the peripheral and central regions. Using long-term lineage tracing, we verified that quiescent corneal epithelial stem cells do exist in the limbal region. While our novel findings require further detailed examination, they may lead to a groundbreaking reconsideration of the corneal-epithelial stem-cell concept.

Research Products

• [Journal Article] Ocular surface reconstruction using stem cell and tissue engineering. (2016)
  • Author(s): Nakamura T，Inatomi T，Sotozono C，Koizumi N，Kinoshita S
  • Journal Title: Progress in Retinal and Eye Research Volume: 51 Pages: 187-207
  • Peer Reviewed
• [Journal Article] Elevated expression of ABCB5 in ocular surface squamous neoplasia. (2016)
  • Author(s): 11.Jongkhajornpong P, Nakamura T, Sotozono C, Nagata M, Inatomi T, Kinoshita S.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 20541-20541
  • DOI: 10.1038/srep20541
  • Peer Reviewed / Open Access
• [Journal Article] OVOL2 maintains the transcriptional program of human corneal epithelium by suppressing epithelial-to-mesenchymal transition. (2016)
  • Author(s): Kitazawa K，Hikichi T，Nakamura T，Sato T，Mitsunaga K，Tanaka A，Nakamura Y，Yamakawa T，Furukawa S，Goshima N，Watanabe A，Okita K，Ueno M，Kawasaki S，Masui S，Kinoshita S
  • Journal Title: Cell Reports Volume: 15 Pages: 1359-1368
  • NAID: 120005753825
  • Peer Reviewed / Open Access
• [Journal Article] Development of functional human oral mucosal epithelial stem/progenitor cell sheets using a feeder-free and serum-free culture system for ocular surface reconstruction. (2016)
  • Author(s): Nakamura T, Yokoo S, Bentley AJ, Nagata M, Fullwood NJ, Inatomi T, Sotozono C, Yamagami S, Kinoshita S
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 37173-37173
  • DOI: 10.1038/srep37173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Development of Functional Human Oral Mucosal Epithelial Stem Cell Sheets Using a Defined, Feeder-free and Serum-free Culture System for Ocular Surface Reconstruction. (2016)
  • Author(s): Nakamura T
  • Organizer: Termis-AP 2016
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2016-09-05
  • Int'l Joint Research
• [Presentation] Loss of human corneal epithelial cell identity exhibited by deletion of PAX6 using the CRISPR/Cas9 system. (2016)
  • Author(s): Kitazawa K，Hikichi T，Nakamura T，Sotozono C，Kinoshita S，Masui S
  • Organizer: 2016 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Seattle，Washington，USA
  • Year and Date: 2016-05-03
  • Int'l Joint Research