Elucidation of mechanisms for transdifferentiation into iHeps

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16461
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyoto University
• Principal Investigator: YASUDA Katsutaro 京都大学, iPS細胞研究所, 特定研究員 (80938621)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: Direct conversion / iHep / iPS細胞

Outline of Final Research Achievements

We conducted functional analysis of transcription factors (Hnf4a, Foxa3, Cebpa, Cebpd, Hnf6 and Onecut2) that we had already identified as master regulators of a mature hepatocyte. We conducted RNA-seq and WGCNA analysis of iHeps which were made by overexpression of various combinations of the 6 factors and searched for hub genes of each module which contains regulatory genes of hepatic functions. As a result, we identified several genes (e.g., Fabp1) as hub genes which are located downstream of the master regulators and we unveiled the existence of hierarchies between the master regulators and their downstream genes.

Free Research Field

肝臓再生医療

Academic Significance and Societal Importance of the Research Achievements

これまで各細胞種には、それらの細胞を特徴づけるマスター転写因子による転写因子ネットワークが存在することが指摘されてきた。一方で、各細胞種の持つ特徴的な機能には、その機能を制御する遺伝子が存在することも指摘されてきた。今回の研究は細胞機能のハブとなる遺伝子をマスター転写因子が制御していることを明らかにした。これらの成果は、細胞種の特徴的な機能の発現を強化したデザイナー細胞の樹立等に応用可能であり、デザイナー細胞を使用した細胞療法の開発に資すると考えられる。