| Project/Area Number |
20K16347
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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 50010:Tumor biology-related
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| Research Institution | Hoshi University (2022-2023)
National Cancer Center Japan (2020-2021) |
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Principal Investigator |
Liu Yuyu 星薬科大学, 先端生命科学研究所, 特任助教 (10870462)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2023: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | Epigenetics / Epigenetic plasticity / gastric stem cell / Gastric stem cell / Gastric mucosa / Gastric stem cells / Aging / Chromatin accessibility / Helicobacter pylori / DNA methylation / Gastric cancer / Single-cell analysis / Stem cell epigenetics |
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| Outline of Research at the Start |
We aim to explain the mechanism in the gastric mucosa where there is a differential targeting for DNA methylation between youngs ter and elderly, and between age-related and inflammation-induced. We hypothesized that there are differences in i) stem and pro genitor cell populations and ii) the epigenome in stem cells. We plan to conduct organoid and single-cell analysis to confirm ou r hypothesis.
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| Outline of Final Research Achievements |
DNA methylation analysis was conducted on gastric mucosa and fibroblasts from 3- and 20-week-old mice, both non-infected and infected with H. pylori (PMSS1) by oral gavage for 2 or 12 weeks. Results showed that the infection induced more aberrant methylation in the gastric mucosa of 3-week-old mice but more aberrant methylation in the fibroblasts of 20-week-old mice after 12 weeks of infection. RNA-seq analysis revealed distinct sets of up-regulated genes in the gastric mucosa and fibroblasts of 3- and 20-week-old mice post-infection.
Additionally, scRNA-seq and scATAC-seq of uninfected mice stomach tissue indicated age-related differential accessible regions enriched in epithelial cells. Moreover, age-related differentially expressed genes were identified in stromal cells with unmodified chromatin accessibility. Furthermore, chromatin regions accessible in a small proportion of 3-week-old stem cells but wholly closed in 20-week-old mice likely reflect youthful epigenetic plasticity.
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| Academic Significance and Societal Importance of the Research Achievements |
This research revealed epigenetic plasticity unique to infant gastric stem cells.
The mechanism of epigenetic plasticity could manifest as: 1) diversity in chromatin accessibility, or 2) the ability to rapidly modify chromatin accessibility.
Further research will aim to elucidate this hypothesis.
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