Establishment and application of the method for inducing human hepatic progenitor cells by direct reprogramming

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H01177
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Kyushu University
• Principal Investigator: Suzuki Atsushi 九州大学, 生体防御医学研究所, 教授 (30415195)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 細胞・組織 / 発生・分化 / 再生医学 / 移植・再生医療 / 遺伝子

Outline of Final Research Achievements

In this study, we identified a specific combination of transcription factors that allow direct reprogramming of human endothelial cells into hepatic progenitor cells. These induced hepatic progenitor cells (iHepPCs) are expandable in monolayer culture and capable of continuously producing functional hepatocytes and cholangiocytes under three-dimensional culture conditions. Also, hiHepPC-derived hepatocytes and cholangiocytes can reconstitute damaged liver tissues and support hepatic function after transplantation. Meanwhile, in the direct reprogramming of mouse fibroblasts to induced hepatocyte-like cells, the integrated analysis of gene expression changes, chromatin state changes, and epigenetic state changes that occur during the process of fibroblasts acquiring hepatic fate has successfully revealed the entire series of dynamic cell state changes starting from the DNA binding of transcription factors that were introduced into fibroblasts.

Free Research Field

発生生物学、再生医学、幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ヒトiHepPCから機能的に成熟した肝細胞や胆管上皮細胞を継続して大量に調達できることから、将来、それらを用いた肝疾患患者に対する新しい移植医療の実現や、個人レベルで薬剤の効果や毒性を評価できる医療システムの構築が期待される。また、マウス線維芽細胞からiHepCへのダイレクトリプログラミングを解析する中で発見したRNAポリメラーゼⅡと転写因子の機能的な結合は、iHepC誘導因子以外の他の転写因子でも起こりうることから、細胞運命制御に関わる転写因子の新しい機能として、今後の研究の発展が期待される。