2023 Fiscal Year Final Research Report
Single-cell transcriptomic and epigenomic analysis of young and elder mouse gastric mucosa infected by Helicobacter pylori
| 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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| Keywords | Epigenetics / Epigenetic plasticity / gastric stem cell |
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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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| Free Research Field |
Epigenetics
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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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