Analysis of master negative regulator Rest as a stem cell regulator by using melanocyte lineage

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08294
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Gifu University
• Principal Investigator: AOKI Hitomi 岐阜大学, 大学院医学系研究科, 講師 (10550361)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 神経分化抑制因子 / Rest / 幹細胞 / 色素細胞

Outline of Final Research Achievements

The neural differentiation inhibitor Rest has various functions other than regulation of neural differentiation, and is involved in maintenance of homeostasis, stress response, carcinogenesis, etc. Rest is expressed in the stem cells in embryos and affects their differentiation, but the function of Rest in adult tissue stem cells is unclear. We previously reported that Rest contributes to the differentiation of neural crest cells into melanocyte stem cells. However, the function of Rest in adult melanocyte stem cells, which influences hair and skin color throughout life, has not been elucidated.
In this study, we analyzed the role of Rest in melanocyte stem cells using an experimental model of age-related hair-graying model and genetically modified mice that can regulate the expression of Rest, and made efforts aimed to elucidate the function of Rest as a differentiation regulator of melanocyte stem cells.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

白髪化は、色素幹細胞やそのニッシェである毛包幹細胞の何らかの異常により生じるが、その発生頻度の高さや心理的な影響の大きさにも関わらず、有効な改善法や効果的な予防法は確立されていない。また、早期白髪化などでの特定の遺伝子が原因である場合を除き、加齢性の白髪化では、その発生や進行、頻度に個人差や人種差が大きく、遺伝的な要因と環境要因などの影響を受けていると思われる。
転写調節因子RestによるMitfを介した色素幹細胞への作用には、エピジェネティックな要因も関連しており、本研究で示された可能性は、将来的な白髪化の予防や改善に貢献する手がかりとなると思われる。