Uncovering beta-cell neogenesis induced by its surrounding niche

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Juntendo University
• Principal Investigator: Miyatsuka Takeshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (60622363)
• Research Collaborator: SASAKI shugo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: β細胞 / シングルセルトランスクリプトーム解析 / トランスクリプトーム解析 / 蛍光イメージング / 糖尿病再生医療

Outline of Final Research Achievements

We developed the novel mouse model “Ins1-eGFP; Timer” that provides spatiotemporal information of newly generated β cells.
Fluorescent imaging revealed that some newborn β cells are detected close to the pancreatic ducts (βduct cells), and unexpectedly, all the other newborn β cells were observed away from the ductal structures and were adjacent to blood vessels (βvessel cells) and pre-existing islets. More βduct cells expressed Mafb, whereas more βvessel cells expressed Mafa, showing distinct characteristics of two cell types of newborn β cells. Furthermore, single-cell RNA sequencing also confirmed transcriptional heterogeneity of newborn β cells.
Collectively, both histological imaging and single-cell transcriptome analysis demonstrated spatial and transcriptional heterogeneity of β-cell neogenesis during development, which will lead to a better understanding of β-cell neogenesis for future cell therapy.

Free Research Field

糖尿病再生医療

Academic Significance and Societal Importance of the Research Achievements

新たに開発したレポーターマウスを用いて生まれたばかりβ細胞を標識しながら蛍光イメージングを行った結果、従来から考えられてきた膵管近傍で生まれる“βduct細胞”以外に、血管近傍で生まれる“βvessel細胞”が存在し、遺伝子発現パターンも異なることが明らかとなった。さらに新生β細胞の遺伝子発現プロファイルを１細胞レベルで解析した結果、新生β細胞は５つのクラスターに細分化されることが示された。
これらの知見が糖尿病根治を目指したβ細胞再生医療に応用されることを期待したい。