Regulatory mechanism of gastric differentiation from gastric stem cells
Project/Area Number |
17H05081
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Gastroenterology
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Research Institution | The University of Tokyo |
Principal Investigator |
Hayakawa Yoku 東京大学, 医学部附属病院, 助教 (60777655)
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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 |
¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2017: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
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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 / アセチルコリン / 遺伝子発現解析 / 内科 / 細胞・組織 / ゲノム / マイクロアレイ / 発生・分化 |
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.
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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。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] GRP30-expressing gastric chief cells do not differentiate but are eliminated via PDK-dependent cell competition during development of metaplasia.2020
Author(s)
1.Hata M, Kinoshita H, Hayakawa Y, Konishi M, Tsuboi M, Oya Y, Hayata Y, Nakagawa H, Tateishi K, Fujiwara H, Hirata Y, Worthley DL, Muranishi Y, Furukawa T, Kon S, Tomita H, Wang TC, Koike K.
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Journal Title
Gastroenterology
Volume: 158
Issue: 6
Pages: 1650-1666
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Three types of metaplasia model through Kras activation, Pten deletion, or Cdh1 deletion in the gastric epithelium.2019
Author(s)
Kinoshita H, Hayakawa Y, Konishi M, Hata M, Tsuboi M, Hayata Y, Hikiba Y, Ihara S, Nakagawa H, Ikenoue T, Ushiku T, Fukayama M, Hirata Y, Koike K.
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Journal Title
Journal of Pathology
Volume: 247
Issue: 1
Pages: 35-47
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mature gastric chief cells are not required for the development of metaplasia.2018
Author(s)
Kinoshita H, Hayakawa Y, Niu Z, Konishi M, Hata M, Tsuboi M, Hayata Y, Hikiba Y, Ihara S, Nakagawa H, Hirata Y, Wang TC, Koike K.
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Journal Title
Am J Physiol Gastrointest Liver Physiol.
Volume: -
Issue: 5
Pages: G583-G596
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Distinct chemopreventive effects of aspirin in diffuse and intestinal-type gastric cancer.2018
Author(s)
Niikura R, Hayakawa Y, Hirata Y, Konishi M, Suzuki N, Ihara S, Yamada A, Ushiku T, Fujishiro M, Fukayama M, Koike K.
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Journal Title
Cancer Prev Res (Phila)
Volume: -
Issue: 5
Pages: 279-286
DOI
Related Report
Peer Reviewed
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[Journal Article] CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric cancer development.2017
Author(s)
Sakitani K, Hayakawa Y, Deng H, Ariyama H, Kinoshita H, Konishi M, Ono S, Suzuki N, Ihara S, Niu Z, Kim W, Tanaka T, Liu H, Chen X, Tailor Y, Fox JG, Konieczny SF, Onodera H, Sepulveda AR, Asfaha S, Hirata Y, Worthley DL, Koike K, Wang TC.
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Journal Title
Oncotarget.
Volume: Nov 10;8(67)
Issue: 67
Pages: 111012-111012
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance.2017
Author(s)
Spechler SJ, Merchant JL, Wang TC, Chandrasoma P, Fox JG, Genta RM, Goldenring JR, Hayakawa Y, Kuipers EJ, Lund PK, McKeon F, Mills JC, Odze RD, Peek RM Jr., Pham T, Que J, Rustgi AK, Shaheen NJ, Shivdasani RA, Souza RF, Storz P, Todisco A, Wang DH, Wright NA.
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Journal Title
Gastroenterology.
Volume: Jul;153(1)
Issue: 1
Pages: e6-e13
DOI
Related Report
Peer Reviewed
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