Single-Cell Transcriptome Analysis of the Replicating Process of Pancreatic Beta Cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21616
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Kyoto University
• Principal Investigator: Inagaki Nobuya 京都大学, 医学研究科, 教授 (30241954)
• Co-Investigator(Kenkyū-buntansha): 臼井 亮太 京都大学, 医学研究科, 特定助教 (40850996) ; 龍岡 久登 京都大学, 医学研究科, 特定助教 (70850981)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 膵β細胞 / 増殖

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. Both transient activation of endoplasmic reticulum stress responders like Atf6 and Hspa5 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.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

糖尿病は進行性の膵β細胞の機能不全および膵β細胞量の低下を病因としている。膵β細胞機能不全についてはこれまで多種の治療薬が開発されている一方で、膵β細胞量を標的にした治療法は確立されていない。本研究により、膵β細胞増殖にはERストレスが関与している可能性が示唆されたことで、今後、膵β細胞増殖制御の分子機構解明、さらには、増殖促進を介した膵β細胞量を標的にした治療法の開発が進むものと期待される。