Elucidation of the mechanism of corneal epithelial development using SEAM as human eye development model
| Project/Area Number |
17K11480
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Osaka University |
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Principal Investigator |
Hayashi Ryuhei 大阪大学, 医学系研究科, 寄附講座教授 (70535278)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 多能性幹細胞 / 角膜上皮 / 表面外胚葉 / ラミニン / BMP / WNT / YAP / 眼発生 / 分化 / ECM / 神経堤 / 角膜 |
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| Outline of Final Research Achievements |
The purpose of this study is to elucidate the signalling mechanisms derived from growth factors and ECMs that contribute to corneal epithelial development by using a human eye development model, SEAM. First, knock-in iPS cell line labelled with EGFP for the p63 gene was established. This KI iPS cell line was used for SEAM induction and demonstrated that in addition to intrinsic BMP-signalling, WNT-signal inhibition is essential for corneal epithelium induction. Regarding ECMs, only laminin isoform 511, which is widely expressed in ocular tissues and has strong integrin-binding capacity was able to induce typical SEAM formation, and that YAP-mediated signals derived from integrin-laminin binding are important for the developmental branching of neuroectoderm and surface ectoderm, including corneal epithelium.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではヒトの眼発生を模倣した細胞モデルであるSEAMを用いて、特に角膜上皮の発生、分化の機序について調べた。角膜上皮は再生医療のための細胞源としてのニーズが高く、我々もiPS細胞を用いた角膜上皮再生医療の開発に取り組んできた。一方で、iPS細胞から角膜上皮を安定的かつ効率的に分化誘導することは容易ではない事も明らかとなってきた。本研究で得られた成果により角膜がどのように発生・分化するのかの理解が深まったことで、角膜上皮を得るための方法が改良され、より安定的かつ効率的に角膜上皮を得ることが可能となった。これにより、再生医療の課題でもあるコスト削減や安全性を高めることが可能になると期待される。
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Cell-Type-Specific Adhesiveness and Proliferation Propensity on Laminin Isoforms Enable Purification of iPSC-Derived Corneal Epithelium.2020
Author(s)
Shibata S, Hayashi R, Kudo Y, Okubo T, Imaizumi T, Katayama T, Ishikawa Y, Kobayashi Y, Toga J, Taniguchi Y, Honma Y, Sekiguchi K, Nishida K.
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Journal Title
Stem Cell Reports.
Volume: 14(4)
Issue: 4
Pages: 663-676
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Generation and validation of a PITX2-EGFP reporter line of human induced pluripotent stem cells enables isolation of periocular mesenchymal cells.2020
Author(s)
Okubo T, Hayashi R, Shibata S, Kudo Y, Ishikawa Y, Inoue S, Kobayashi Y, Honda A, Honma Y, Kawasaki S, Nishida K.
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Journal Title
J Biol Chem.
Volume: 295
Issue: 11
Pages: 3456-3465
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] elective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages.2018
Author(s)
Shibata S, Hayashi R*, Okubo T, Kudo Y, Katayama T, Ishikawa Y, Toga J, Yagi E, Honma Y, Quantock AJ, Skiguchi K and Nishida K.
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Journal Title
Cell Rep.
Volume: 6;25(6)
Issue: 6
Pages: 1668-1679
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Cell-Type-Specific Adhesiveness and Proliferation Propensity on Laminin Isoforms Enable Purification of iPSC-Derived Corneal Epithelium2020
Author(s)
Shibata S, Hayashi R, Kudo Y, Okubo T, Imaizumi T, Katayama T, Ishikawa Y, Kobayashi Y, Toga J, Taniguchi Y, Honma Y, Sekiguchi K, Nishida K
Organizer
Gordon Conference Ocular Surface Biology and Pathology
Related Report
Int'l Joint Research
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[Presentation] PURIFICATION OF HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED CORNEAL EPITHELIAL CELLS USING CELL TYPE-SPECIFIC ADHESIVENESS ON LAMININ ISOFORMS2019
Author(s)
Shun Shibata, Ryuhei Hayashi, Yuji Kudo, Toru Okubo, Tomohiko Katayama, Yuki Ishikawa, Yuki Kobayashi, Junko Toga, Yukimasa Taniguchi, Yoichi Honma, Kiyotoshi Sekiguchi, & Kohji Nishida
Organizer
International Society for Stem Cell Research 2019, Annual Meeting
Related Report
Int'l Joint Research
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[Book] 眼科2017
Author(s)
林 竜平
Total Pages
8
Publisher
金原出版
Related Report
