The novel differentiation method in pluripotent stem cells without using gene introduction or cytokine stimulation.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H04510
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Tohoku University
• Principal Investigator: Dezawa Mari 東北大学, 医学系研究科, 教授 (50272323)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Muse細胞 / 多能性幹細胞 / 貪食 / 単一細胞遺伝子発現解析 / マクロファージ

Outline of Final Research Achievements

A novel mechanism for somatic stem cell differentiation via phagocytosing apoptotic differentiated cells was found to require only a short time frame. Pluripotent Muse cells phagocytosed apoptotic differentiated cells. The phagocytosed-differentiated cell-derived contents (e.g., transcription factors) were quickly translocated into the nucleus, and led to differentiation initiation. The gene expression profiles were similar to those of the authentic differentiated cells and expressed functional markers in single cell RNA sequencing. iPS/ES cells did not show phagocytosis-induced differentiation activity. Together, our findings uncovered a simple mechanism by which differentiation-directing factors are directly transferred to somatic stem cells by phagocytosing apoptotic differentiated cells to trigger their rapid differentiation into the target cell lineage.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

これまで細胞分化は遺伝子導入やサイトカイン刺激など、外からの因子が加わることで制御されると長らく考えられてきた。また貪食というのは、マクロファージに代表されるように異物や死細胞などの残骸を掃除するための免疫的な機能として理解されてきた。本実験によって貪食は単にゴミ掃除ではなく、分化に必要な因子を素早く無駄なく獲得し、同じ細胞種に迅速分化するという全く新しい生物学的機能を発見することに繋がった。