Characteristics of induced pluripotent stem cells from clinically divergent female monozygotic twins with Danon disease.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19632
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kanazawa University
• Principal Investigator: Yoshida Shohei 金沢大学, 附属病院, 助教 (30623657)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ダノン病 / iPS細胞 / オートファジー / X染色体不活性化

Outline of Final Research Achievements

We successfully established two sets of induced pluripotent stem cell(iPSC) lines and iPSC derived cardiomyocyte(iPSC-CMs) subseqently, that expressed either wild-type or mutant LAMP2 allele from female with danon disease, of which only the populations expressing mutant LAMP2 showed autophagic failure. By means of androgen receptor methylation assays, we revealed that the XCI patterns of the iPSCs elucidate the LAMP2 expression and subsequent in vitro phenotype. The in vitro characteristics of generated iPSCs and iPSC-CMs did not rely on the clinical phenotype.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

ダノン病女性患者から疾患特異的な表現型を持つiPS細胞と持たないiPS細胞を作成し、心筋に分化させることに成功した。本研究の結果は、逆に表現型を持たないが、遺伝子変異を持ついわゆるキャリアから疾患特異的なiPS細胞が作成できる可能性を示唆している。また、本研究成果はその他のX連鎖性の疾患にも応用することができる。加えて常染色体遺伝性の疾患の疾患特異的iPS細胞を作成する際にX染色体の異常にも配慮する必要性を示唆した。