Regulatory mechanism of gastric differentiation from gastric stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H05081
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Hayakawa Yoku 東京大学, 医学部附属病院, 助教 (60777655)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 胃上皮幹細胞 / 萎縮性胃炎 / 粘膜再生 / 腸上皮化生 / 分化 / 胃癌

Outline of Final Research Achievements

We performed gene expression analysis of gastric stem cells, progenitors, and other mature cell types, and identified novel markers specific for each cell population. We generated several mouse lines that mark these specific cell types. We analyzed histological and molecular changes in stem and other cell types during early carcinogenesis, and identified the mechanism of the development of gastric metaplasia and cancer. We also showed that tuft cell-mediated acetylcholine signal is important for stem cell function and mucosal regeneration via ERK pathway, and identified several chemicals that revert the gastric precancerous change, loss of parietal cells.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

新規の胃上皮幹細胞マーカーの同定とその制御機構を解明したことにより、胃発癌や粘膜再生のメカニズムを明らかにすることに貢献した。
胃癌や腸上皮化生は成熟細胞ではなく幹細胞・前駆細胞から発生することが明らかになり、より選択的な治療標的の同定や、発癌予測のバイオマーカーの樹立に役立つ可能性がある。
Tuft細胞や壁細胞の分化制御機構やその粘膜再生における機能を明らかにしたことで、今後の胃癌に対する予防や治療の開発に結びつく可能性がある。