Understanding molecular mechanisms controlling incretin-induced beta cell proliferation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09825
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gifu University (2018-2019); Kyoto University (2017)
• Principal Investigator: Daisuke Yabe 岐阜大学, 大学院医学系研究科, 教授 (60378643)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 膵β細胞 / 増殖 / 老化 / シングルセルRNA-Seq

Outline of Final Research Achievements

Heterogeneity of gene expression and rarity of replication hampers molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in a sequence of replication process of the β-cell by single-cell RNA sequencing of islets in young and old mice after partial pancreatectomy, which identified 4 subpopulations of Ins1-expressing β-cells (Clusters 1-4). We identified the Cluster 4 cells as replicating β-cells with high expression of cell proliferation markers. A pseudo-time course analysis demonstrated cell cycle progression with switching expression of cyclins and grasped transient activation of ER stress responders and tumor suppressors, giving fine balance of cell cycle progression and arresting. Motif analysis supported change of gene network was regulated by critical transcription factors.In addition, we developed a novel tool that specifically labels replicating β cells.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

糖尿病は膵β細胞の機能不全および膵β細胞量の低下を病因とし、その克服は世界的に最も重要な課題である。今回、膵β細胞量の制御機構の一部を明らかにすることができ、今後、膵β細胞量を標的にした糖尿病の発症予防および治療法の確立に大きく貢献するものと期待される。