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携带与降低阿尔茨海默病风险相关的淀粉样前体蛋白杂合A673T变体的人诱导多能干细胞系(UEFi003-A)的产生。

Generation of a human induced pluripotent stem cell line (UEFi003-A) carrying heterozygous A673T variant in amyloid precursor protein associated with a reduced risk of Alzheimer's disease.

作者信息

Rolova Taisia, Wu Ying-Chieh, Koskuvi Marja, Voutilainen Jenni, Sonninen Tuuli-Maria, Kuusisto Johanna, Laakso Markku, Hämäläinen Riikka H, Koistinaho Jari, Lehtonen Šárka

机构信息

Neuroscience Center, University of Helsinki, Helsinki, Finland.

Neuroscience Center, University of Helsinki, Helsinki, Finland; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

出版信息

Stem Cell Res. 2020 Oct;48:101968. doi: 10.1016/j.scr.2020.101968. Epub 2020 Sep 2.

Abstract

A673T mutation in the amyloid precursor protein (APP) is a rare variant associated with a reduced risk of late-onset Alzheimer's disease (AD) and age-related cognitive decline. The A673T mutation decreases beta-amyloid (Aβ) production and aggregation in neuronal cultures in vitro. Here we have identified a Finnish non-diseased male individual carrying a heterozygous A673T mutation, obtained a skin biopsy sample from him, and generated an iPSC line using commercially available integration-free Sendai virus-based kit. The established iPSC line retained the mutation, expressed pluripotency markers, had a normal karyotype, and differentiated into all three germ layers in vitro.

摘要

淀粉样前体蛋白(APP)中的A673T突变是一种罕见的变异,与晚发性阿尔茨海默病(AD)风险降低及年龄相关的认知衰退有关。A673T突变在体外神经元培养中可减少β淀粉样蛋白(Aβ)的产生和聚集。在此,我们鉴定出一名携带杂合A673T突变的芬兰非患病男性个体,从他身上获取了皮肤活检样本,并使用市售的无整合仙台病毒试剂盒生成了诱导多能干细胞(iPSC)系。所建立的iPSC系保留了该突变,表达多能性标志物,具有正常核型,并在体外分化为所有三个胚层。

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