Study on the mechanism of cell fate decisions by histone lactylation in mesenchymal stem cell differentiation.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16936
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Showa University
• Principal Investigator: SASA KIYOHITO 昭和大学, 歯学部, 助教 (50823069)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: osteoblast / lactylation / differentiation

Outline of Final Research Achievements

Modification of histones plays an important role in regulating changes in the higher-order structure of chromosomes, transcriptional regulation, maintenance of cell fate, and the like through various chemical modifications. In recent years, lactylation by lactic acid was discovered as a new modification of histones and has attracted worldwide attention. To date, we have discovered a new function of MCTs: lactate transport by MCT1 regulates the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. In this study, we will clarify how histone lactylation by lactate affects the differentiation of mesenchymal stem cells. The results of this study will lead to the elucidation of a new differentiation mechanism by lactylation of lactic acid, and may greatly contribute to the development of new therapeutic methods for bone metabolism diseases.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

乳酸によるヒストン修飾であるラクチル化が骨芽細胞の分化を促進する可能性が示唆された。乳酸は、ほとんどの組織内で産生される物質であり、生体の局所的な応用がしやすい分子であると考えられる。今後のヒストンラクチル化が制御する遺伝子や調節する酵素を詳細に調べることで、新たな骨代謝疾患の標的となる可能性がある。