Identification of molecular mechanisms in the wound associated reprogramming of intestinal epithelial cells
| Project/Area Number |
18K15743
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Yui Shiro 東京医科歯科大学, 統合研究機構, 講師 (00383886)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 腸上皮再生機構 / 腸上皮オルガノイド / I型コラーゲン / 胎児腸上皮細胞 / 数理モデル / 上皮移植モデル / FEnS / Mathematical modeling / Transplantation / Lgr5 positive stem cells / 胎児型上皮への運命転換 / 上皮傷害 / リプログラミング |
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| Outline of Final Research Achievements |
In this project, we identified the dynamic fate change of intestinal epithelial cells upon tissue injury, which secures the effective regenerative process of intestine. This fate change can be referred as fetalization, in which maturate adult intestinal epithelial cells are temporally reprogrammed into fetal-type epithelial cells. Importantly, this project definitely offered the molecular basis of fetaliztion in the activation of transcriptional factors YAP/TAZ in extracellular matrix dependent manner. In order to understand the regenerative response in more details, we also analyzed the developmental process of intestine using mathematical modeling as well as transplantation assay, and identified the equal potential of all different fetal epithelial progenitors to maturate adult stem cells. All these results clearly provide the scheme to understand the outstanding regenerative capacity of intestine from its molecular mechanisms in line with developmental process.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、腸という個体内でも突出した再生能力を備えた臓器の特性を明らかにする学術的に重要な研究である。組織の再生における胎児化の機構や、その過程における細胞外基質の役割を当該研究領域で初めて明らかにした研究成果である。すでに腸管における同様の機構に関する報告だけでなく、神経組織や肝組織の再生にも類似した機構があることが報告されるなど、組織再生に関わる基礎研究の重要なテーマとなっている。本研究は、細胞に若返る能力があるというメッセージを有しており、このメッセージは広く社会的な反響を惹起しうるものであると考えている。
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Organoid-based regenerative medicine for inflammatory bowel diasease.2020
Author(s)
Okamoto R, Shimizu H, Suzuki K, Kawamoto A, Takahashi J, Kawai M, Nagata S, Hiraguri Y, Takeoka S, Sugihara HY, Yui S, Watanabe M
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Journal Title
Regen Ther.
Volume: 13
Pages: 1-6
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Tracing the origin of adult intestinal stem cells2019
Author(s)
Jordi Guiu, , Shiro Yui, Samuel Martti Maimets, Perlman, Lene Lundvall, Linn Salto Mamsen, Agnete Larsen, Rasmus H Olesen, Claus Yding Andersen, Lea Langhoff Thuesen, Kristine Juul Hare, Tune H Pers, Benjamin D Simons, Kim B Jensen et al.
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Journal Title
Nature
Volume: 570
Issue: 7759
Pages: 107-111
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Conceptual basis of lineage shift between intestinal epithelium and hepatocytes2020
Author(s)
Sakurako Kobayashi, Satoshi Watanabe, Yosuke Yoneyama, Kousuke Tanimoto, Ryu Nishimura, Sayaka Nagata, Masami Inoue, Kouhei Suzuki, Sei Kakinuma, Kiichiro Tsuchiya, Ryuichi Okamoto, Mamoru Watanabe, Takanori Takebe, Shiro Yui
Organizer
Keystone Symposia, Tissue Organoids as Models of Host Physiology and Pathophysiology of Disease
Related Report
Int'l Joint Research
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