Elucidation of the molecular mechanism of skewed X chromosome inactivation associated with X-linked diseases.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Institute for Developmental Research Aichi Developmental Disability Center
• Principal Investigator: KATOH Kimiko 愛知県医療療育総合センター発達障害研究所, 障害モデル研究部, 研究員 (30598602)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: X連鎖性疾患 / X染色体不活性化

Outline of Final Research Achievements

Because XY males have a single X chromosome, whereas XX females have two of them, to ensure dosage compensation between females and males, one of the two X chromosomes is chosen for silencing (X chromosome inactivation, XCI). This machinery is tightly regulated, and its dysregulation leads to the development of various diseases involving the X chromosome. In this study, we aimed to elucidate the molecular mechanisms of XCI dysregulation in X-linked diseases using patient-derived iPS cells. As a result, we found several groups of molecules which were suggested to be related to dysregulation of XCI.

Free Research Field

胎児医学

Academic Significance and Societal Importance of the Research Achievements

近年、多能性幹細胞を用いたヒト初期胚モデルの作製の報告が相次いでおり、着床前後の初期胚における遺伝子発現変動が明らかになってきた。しかし、X連鎖性疾患の女性患者でskewed XCIが生じやすくなる原因については、未だ不明である。本研究により、患者でskewed XCIが確立する機構を解明できれば、ヒトのXCIの機構のみならず、X連鎖性疾患の理解に大きな前進をもたらす意義深い研究になると考えられる。さらにこの知見は、X連鎖性疾患の新たな予測・診断・治療法の創出につながる可能性がある。