The First Hospital of Qin Huangdao, QinHuangdao, Hebei Province 066000, China; Hebei Medical University-Galway University Stem Cell Research Center, Hebei Medical University, Shijiazhuang, Hebei Province 050017, China.
Hebei Medical University-Galway University Stem Cell Research Center, Hebei Medical University, Shijiazhuang, Hebei Province 050017, China; Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Province 050017, China; Hebei Technology Innovation Center for Stem Cell and Regenerative Medicine, Hebei Province, China; Hebei International Joint Research Center for Stem Cell and Regenerative Medicine, Hebei Province, China.
Stem Cell Res. 2024 Oct;80:103506. doi: 10.1016/j.scr.2024.103506. Epub 2024 Jul 28.
The APOE 4 allele remains the primary genetic risk factor for sporadic Alzheimer's disease, whereas the APOE 2 allele emerges as a protective factor. Therapeutic approaches in murine models with human APOE alleles, such as modulating APOE levels and converting isoforms, show efficacy. However, there is a lack of in vitro APOE2-mutant human neuronal models. Hence, in this study, we generated human induced pluripotent stem cells (hiPSCs) from the peripheral blood mononuclear blood cells (PMBC) of a 42-year-old female donor carrying the APOE-ε2/ε2 allele. The newly generated hiPSC displayed normal karyotype and could differentiate into three germ layers. Besides, they retained their original genotype and expressed pluripotency markers.
载脂蛋白 E4 等位基因仍然是散发性阿尔茨海默病的主要遗传风险因素，而载脂蛋白 E2 等位基因则表现出保护作用。在携带人类载脂蛋白 E 等位基因的小鼠模型中，如调节载脂蛋白 E 水平和转换异构体等治疗方法显示出疗效。然而，目前缺乏体外载脂蛋白 E2 突变型人类神经元模型。因此，在本研究中，我们从携带载脂蛋白 E-ε2/ε2 等位基因的 42 岁女性供体的外周血单核细胞（PMBC）中生成了人类诱导多能干细胞（hiPSC）。新生成的 hiPSC 显示正常核型，并能分化为三个胚层。此外，它们保留了原始基因型并表达多能性标志物。
