<title_ja>患者iPS細胞由来分化神経細胞を用いた自閉スペクトラム症関連遺伝子<i>POGZ</i>の機能解析</title_ja> <title_en>Functional Analysis of the Autism Spectrum Disorder-Associated Gene Product, POGZ Using Patient-Derived iPS Neurons</title

2-B-P-079 <title_ja>患者iPS細胞由来分化神経細胞を用いた自閉スペクトラム症関連遺伝子<i>POGZ</i>の機能解析</title_ja> <title_en>Functional Analysis of the Autism Spectrum Disorder-Associated Gene Product, POGZ Using Patient-Derived iPS Neurons</title_en> 〇鮎澤有希子¹、河野翔太郎¹、大友愛佳¹、片山沙香¹、濱田萌々子¹、福島穂高¹、三浦大樹¹、橋本均^2,3,4,5,6,7、橋本亮太³、中澤敬信^1,3 Yukiko Ayusawa¹, Shotaro Kawano¹, Manaka Otomo¹, Sayaka Katayama¹, Momoko Hamada¹, Hotaka Fukushima¹, Daiki Miura¹, Hitoshi Hashimoto^2,3,4,5,6,7, Ryota Hashimoto³, Takanobu Nakazawa^1,3 ¹東農大・院生命・バイオ・動物分子生物、²阪大・院薬・神経薬理、³国立精神・神経医療研究セ・精神保健・精神疾患病態、⁴阪大・院連合小児発達学研・附属子どものこころの分子統御機構研究セ、⁵阪大・データビリティフロンティア、⁶阪大・先導的学際研、⁷阪大・院医・分子医薬 ¹Lab. Mol. Biol., Dept. of Biosci., Grad. Sch. of Life Sci., Tokyo Univ. Agr., ²Dept. of Neuropharmacol., Grad. Sch. Pharmaceut., Osaka Univ., ³Dept. Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, ⁴United Grad. Sch. Child Dev., Osaka Univ., ⁵Div. Biosci., Inst. Datability Sci., Osaka Univ., ⁶Transdimensional Life Imaging Div., Inst. Open Transdiscip. Res. Initiatives, Osaka Univ., ⁷Dept. Mol. Pharmaceut., Grad. Sch. Med., Osaka Univ. Autism Spectrum Disorders (ASDs) are likely to be associated with impaired central nervous development, however the molecular and cellular pathogenesis of ASDs remains largely unknown. In this study, we focused on POGZ, one of the most recurrently mutated genes in patients with ASDs. To elucidate the molecular and cellular pathogenesis underlying POGZ mutation-mediated neural developmental abnormalities, comprehensive RNA expression analysis was conducted using samples derived from neural stem cells and neurons from a patient with POGZ mutation and control individuals. We performed gene ontology (GO) enrichment analysis on genes that exhibited significant differences in expression between patients and healthy individuals and found that the differentially expressed genes in neural stem cells and neurons were enriched for GO terms involving neural development. Furthermore, phospho-proteome analysis suggested that several signal transduction pathways potentially implicated in neural development were impaired in iPS cell-derived neurons from the patient. Our current results will help to clarify the pathogenesis of the de novo mutation in the POGZ gene locus, providing crucial insights into understanding the molecular and cellular pathogenesis underlying ASDs.