Establishment of a new differentiation conversion method to mature pancreatic beta cells by analysis of gene expression over time during differentiation process

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16209
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kagoshima University
• Principal Investigator: MATSUDA Eriko 鹿児島大学, 医歯学域医学系, 助教 (20815914)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ダイレクトリプログラミング / 再生医療 / β細胞 / 糖尿病

Outline of Final Research Achievements

Direct reprogramming is expected to be developed as a curative therapy for diseases of organs and cells that do not retain the ability to regenerate on their own. Although there have been reports on the conversion of β cells to functional glucose-responsive cells by direct reprogramming as a curative therapy, the creation of functional β cells has not yet been achieved. The search for and analysis of new differentiation factors are necessary for the differentiation conversion to functionally mature β-cells. To elucidate a part of the process of functional maturation of β cells, we verified the function of ACT-SC reporter cells used for temporal gene expression analysis, and obtained unexpected results in transgene expression in specific safety regions.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

1型糖尿病は自己免疫反応によるβ細胞の破壊によって引き起こされ、重度の高血糖を引き起こす。治療の主体はインスリン療法のみであるため、β細胞量を維持・回復するための介入方法の開発が求められている。β細胞など自立再生能を保持しない臓器・細胞の疾患の根治療法として発展が期待されるDR法は誘導効率が低いため、機能的に成熟したβ細胞への分化転換には新たな分化転換因子の探索と解析が必要である。ヒトES/iPS細胞から目的細胞への分化段階に応じた遺伝子発現解析法を確立させることは、新規分化転換因子の獲得を可能とし、DR法による目的細胞への分化転換効率の改善と、成熟β細胞への分化転換法の確立に貢献できる。