Etiological research of developmental disorders in sexual chromosome abnormalities

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10386
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Sato Hiroshi 九州大学, 歯学研究院, 助教 (00421313)
• Co-Investigator(Kenkyū-buntansha): 加藤 大樹 九州大学, 歯学研究院, 助教 (30452709) ; 増田 啓次 九州大学, 大学病院, 講師 (60392122)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 歯髄幹細胞 / 染色体異常 / クラインフェルター症候群 / 神経分化 / ミトコンドリア

Outline of Final Research Achievements

Klinefelter's syndrome (KS), develops in men with extra X chromosomes, presents with hypogonadism and cognitive impairment. However, the etiology behind cognitive impairment is as yet not well understood. In this study, stem cells from human exfoliated deciduous tooth (SHED) harboring extra X chromosomes were prepared from dental pulp of KS children with cognitive impairment. Neurons induced from KS-SHED showed impaired neuronal differentiation. Analysis of mitochondria, which affect neural differentiation, revealed reduced mitochondrial protein levels and lower membrane potentials in KS compared to controls. Decreased expression of SIRT1 gene in KS-SHED might be related with lower mitochondrial activity and abnormal neuronal differentiation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

調整や神経分化が容易なSHEDを染色体の異常を保ったままクラインフェルター患児から分離できたことは、発達障害の病態解明の資源としての役割は大きい。また、本実験ではこれを用いてクラインフェルター症候群の神経において,発達の異常とタンパク質減少を伴うミトコンドリア活性の低下を始めて明らかとした。さらに、ミトコンドリアと関係のあるSIRT1を始めとするいくつかの遺伝子の発現の変化を明らかとしており、病態の解明と薬剤の選択の糸口となることが期待される。