Pathophysiological analysis of congenital myasthenia syndrome and other disorders using human neuromuscular junction models

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03642
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto University
• Principal Investigator: Saito Megumu 京都大学, iPS細胞研究所, 教授 (90535486)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 脊髄性筋萎縮症 / SMN / iPS細胞 / 骨格筋 / miRNA / ミトコンドリア / 転写制御 / 先天性筋無力症候群

Outline of Final Research Achievements

We succeeded in constructing an in vitrol model of congenital myasthenia syndrome (CMS) by using human induced pluripotent stem cells (iPS cells). We also constructed a model of skeletal muscle lesions in spinal muscular atrophy (SMA) and found that cells lacking SMN, the gene responsible for SMA, have abnormal mitochondrial function during muscle differentiation, resulting in impaired muscle differentiation due to abnormal energy metabolism and excessive production of reactive oxygen species. We also found that SMN localizes into the nucleus during muscle differentiation, binds to the genome, and is involved in the transcriptional regulation of several muscle differentiation-related factors, including miRNAs.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、CMSの病態モデル構築に成功した。また、SMAの骨格筋病変の発症機構の１つが明らかになった。SMNの新しい機能として、SMNがゲノム上で特定の転写因子と相互作用し、その標的遺伝子の発現調節に関与している可能性を示した。これらの成果は、ヒト体細胞における細胞種特異的な遺伝子転写制御の一端を明らかにし、骨格筋を標的としたSMAの新規治療法の可能性を提示するものである。