Mechanism of tissue interaction in human eye development.
| Project/Area Number |
19H01063
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
Nishida Kohji 大阪大学, 医学系研究科, 教授 (40244610)
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| Co-Investigator(Kenkyū-buntansha) |
辻川 元一 大阪大学, 医学系研究科, 教授 (70419472)
林 竜平 大阪大学, 医学系研究科, 寄附講座教授 (70535278)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2021: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2020: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2019: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
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| Keywords | オルガノイド / 再生医療技術 / 順遺伝学 / 眼発生異常 / PAX6 / 器官発生 / iPS細胞 / SEAM / 疾患特異的 / 幹細胞 / SEAM法 |
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| Outline of Research at the Start |
マウスなどの解析により組織発生メカニズムについては近年理解が深まったが、ヒトに
おける器官形成については未だほとんどが未知である。ヒトにおける発生系譜の異なる多くの組織が集合して形成される器官モデルが存在せず、発生期の各組織の相互作用のあり方が不明であるためである。我々はヒトiPS細胞から目に関する組織原器すべてが発生し、さらにそれが自律的に同心円状の構造を形成するSEAM法という誘導法を開発した（Nature2016）。このSEAMを用いて現在不明である器官形成時における各発生系譜の相互作用と形の形成分子メカニズムについて検討を行い、病変部位における器官構築という新たな再生医療開発につなげる。
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| Outline of Final Research Achievements |
We had tried to elucidate the crosstalk mechanism of each tissue during human organogenesis. Specifically, we examined the mechanism by which SEAM itself is generated. In SEAM, cells and tissue primordia with different developmental genealogy are arranged concentrically.
Mutation induction by ENU (N nitrosourea) in iPS cells was performed last year to obtain many mutant strains, and then SEAM induction was performed on each of them, and 92 strains causing the abnormality were identified. These abnormalities are classified into about 5 patterns according to the phenotype, and we perform a whole-genome sequence for those that are abnormal due to poor occurrence of 2 layers and those that cause abnormalities in the shape of 3 layers.This was compared with the genomic annotations up to now, and the analysis was started in order from the one that seems to be the causative gene mutation, and the knockout form by CRSPR was analyzed for one gene and mRNAseq was performed.
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| Academic Significance and Societal Importance of the Research Achievements |
本検討に於いてはヒトの器官形成における初めてのミュータジェネシススクリーニング系を確立したと考えている。従来に於いて、ヒトを用いた、眼のような複雑な発生過程をを持つ器官全体の発生を検討することはできなかった。本検討に於いては再生医療技術を応用することで、極めて基礎的な研究にその成果を還元できることを示したものと思われる。また、作製したライブラリーを順次解析することで人の眼の発生の機構をこれからも明らかにしていくことが期待できる
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Report
(5 results)
Research Products
(57 results)
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[Journal Article] Chondroitin Sulfate as a Potential Modulator of the Stem Cell Niche in Cornea.2021
Author(s)
Ashworth S, Harrington J, Hammond G.M., Bains K.K, Koudouna E, Hayes A. J., Ralphs J.R., Regini J.W., Young R.D, Hayashi R, Nishida K.
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Journal Title
Front. Cell Dev. Biol.
Volume: 12
Pages: 12-12
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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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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[Presentation] HLA 6 loci matched allogeneic iPS cells derived retinal pigment epithelial cells (iPSC-RPE) transplantation.2019
Author(s)
Masayo Takahashi, S. Sugita, M. Mandai, Y. HIrami, S. Takagi, M. Yamamoto, N. Koide, H. Sakaguchi, K. Maruyama, K. Nishida, S. Yamanaka, Y. Kurimoto.
Organizer
ARVO Annual Meeting 2019
Related Report
Int'l Joint Research
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