2021 Fiscal Year Final Research Report
Single-Cell Transcriptome Analysis of the Replicating Process of Pancreatic Beta Cells
| Project/Area Number |
20K17531
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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 54040:Metabolism and endocrinology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 膵β細胞 / 増殖 |
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| Outline of Final Research Achievements |
Heterogeneity of gene expression and rarity of replication hamper molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in β-cell replication process by single-cell RNA sequencing of murine pancreas with or without partial pancreatectomy. We observed heterogeneity of Ins1-expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers Pcna and Mki67. We also recapitulated cell cycle transition accompanied with switching expression of cyclins and E2F transcription factors. Both transient activation of endoplasmic reticulum stress responders and elevated expression of tumor suppressors and DNA damage responders during the transition to replication associated fine balance of cell cycle progression and protection from DNA damage. Taken together, these results provide a high-resolution map depicting a sophisticated genetic circuit for replication of the β-cells.
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| Free Research Field |
糖尿病学
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病状態ではインスリンを産生する膵β細胞の量が少なくなることから，その再生を誘導する治療法の確立が期待されている。一方で，β細胞以外にも複数の内分泌細胞がある膵臓では，β細胞だけに注目して解析することが困難であった。本研究では，β細胞の増殖が促されるモデルマウスの膵臓について，一細胞レベルで遺伝子発現を観察するシングルセルRNAシークエンスを行い，β細胞の増殖過程の詳細を解析した。遺伝子発現プロファイルから細胞状態の遷移を解析する擬似時系列解析によって，増殖停止期から増殖期への遷移に関与する遺伝子群を捉え、膵β細胞が増殖するプロセスを一細胞レベルで解析することに成功した。
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