Division of Pediatric Epileptology, Center for Pediatrics and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Department of Human Genetics, Hannover Medical School (MHH), 30625 Hannover, Germany.
Stem Cell Res. 2022 Jul;62:102818. doi: 10.1016/j.scr.2022.102818. Epub 2022 May 24.
Variants in different neuronal tubulin isotypes cause severe neurodevelopmental disorders with cerebral malformations accompanied by developmental delay, motor impairment, and epilepsy, known as tubulinopathies. Induced pluripotent stem cells were generated from peripheral blood mononuclear cells from a female subject carrying the heterozygous de novo variant c.[521C > T] (p.[Ala174Val]) in the TUBA1A gene. PBMCs were reprogrammed using the CytoTune™-iPS 2.0 Sendai Reprogramming Kit (Invitrogen) and showed a normal karyotype, expression of pluripotency markers, and spontaneous in vitro differentiation into all three germ layers. The generated iPSCs represent a useful tool to study the pathophysiology of TUBA1A tubulinopathy.
不同神经元微管蛋白异构体的变异导致严重的神经发育障碍，伴有脑畸形、发育迟缓、运动障碍和癫痫，称为微管病。从携带异质从头变异 c.[521C>T]（p.[Ala174Val]）的女性外周血单核细胞中生成诱导多能干细胞 TUBA1A 基因。使用 CytoTune™-iPS 2.0 Sendai 重编程试剂盒（Invitrogen）对 PBMC 进行重编程，显示正常核型、多能性标记物的表达，并自发体外分化为三个胚层。生成的 iPSCs 是研究 TUBA1A 微管病病理生理学的有用工具。
