Identification of genomic changes and their therapeutic effects in neuronally-differentiated induced pluripotent stem cells of autistic patients

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670473
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: University of Yamanashi
• Principal Investigator: KUBOTA Takeo 山梨大学, 総合研究部, 教授 (70293511)
• Co-Investigator(Kenkyū-buntansha): TOYODA Atsushi 国立遺伝学研究所, 生物遺伝資源情報総合センター, 特任准教授 (10267495)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: エピジェネティクス / エピゲノム / 治療薬 / iPS細胞 / レット症候群 / 自閉症 / 遺伝子発現制御 / バルプロ酸ナトリウム

Outline of Final Research Achievements

We investigated abnormalities in the neuronal cells differentiated from the induced pluripotent stem cells (iPSC) derived from Rett syndrome patients, a representative autistic disorder caused by MECP2 mutations. As a result, we found abnormal expression of astrocyte-specific genes. Furthermore, we found that the chemicals, target to HDAC and Sin3 which are parts of MeCP2 protein complex, up-regulated Rett syndrome- and autism-associated genes. These findings suggest that malfunction of MeCP2-induced genomic changes may underlie the alteration of astrocyte-specific genes, and indicate that the chamicals examined possibly recover the gene expression which were down-regulated in Rett and autistic patients.

Free Research Field

エピジェネティクス