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Elucidating the regulatory mechanisms of intestinal epithelial cell dedifferentiation during intestinal stem cell injury

Research Project

Project/Area Number 21K15132
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44040:Morphology and anatomical structure-related
Research InstitutionHokkaido University (2023)
Saitama University (2021-2022)

Principal Investigator

Takemi Shota  北海道大学, 先端生命科学研究院, 特任助教 (70871440)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords腸上皮幹細胞 / 脱分化 / オルガノイド / 腸オルガノイド / 腸幹細胞 / パネート細胞 / 幹細胞
Outline of Research at the Start

小腸の陰窩底部に位置する幹細胞が傷害を受け死滅すると、腸幹細胞付近に位置する分化細胞は脱分化を引き起こし、幹細胞様の性質を獲得して上皮再生に寄与する。腸の分化細胞がどのように脱分化を引き起こすのか、その機序はほとんど不明である。本研究は、腸幹細胞の3次元培養により生体構造を模した「腸オルガノイド」を用いて分化細胞の脱分化の分子機構を明らかにする。

Outline of Final Research Achievements

It is known that when stem cells located at the base of the crypts of the small intestine are injured and die, differentiated cells located near intestinal stem cells cause dedifferentiation, acquire stem cell-like properties and contribute to epithelial regeneration, but the mechanism of how intestinal differentiated cells cause dedifferentiation is largely unknown. Therefore, the aim of this study was to elucidate the molecular mechanisms of the dedifferentiation of Panete cells using intestinal organoids. In this study, the laser power of the femtosecond laser and the time at which it was applied to the cells were optimised, and a system was constructed to observe the behaviour of the cells.

Academic Significance and Societal Importance of the Research Achievements

小腸幹細胞が傷害を受け死滅すると引き起こされる分化細胞の脱分化は上皮再生に寄与することが知られており、この脱分化機構の破綻はがんや炎症といった疾病につながるため、脱分化制御の機構を解明することは重要である。本研究では、この脱分化機構の解明につながる基礎的な研究成果を生み出すものである。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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