Schuster Stefanie, Schelling Yvonne, Synofzik Matthis, Höflinger Philip, Schöls Ludger, Hauser Stefan
Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, Tübingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Stem Cell Res. 2018 May;29:166-169. doi: 10.1016/j.scr.2018.04.001. Epub 2018 Apr 9.
STUB1/CHIP is a central component of cellular protein homeostasis and interacts with key proteins involved in the pathogenesis of many neurodegenerative diseases. Here, we reprogrammed human skin fibroblasts from a 12-year-old male patient with recessive spinocerebellar ataxia type 16 (OMIM #615768), carrying compound heterozygous mutations (c.355C>T, c.880A>T) in STUB1. Genomic integrity of the iPSC line HIHCNi001-A without transgene integration and genomic aberration but with maintained disease-relevant mutations was proven by SNP array analysis and Sanger sequencing while pluripotency was verified by the expression of important pluripotency markers and the capacity to differentiate into cells of all three germ layers.
STUB1/CHIP是细胞蛋白质稳态的核心组成部分，与许多神经退行性疾病发病机制中涉及的关键蛋白质相互作用。在此，我们对一名患有隐性16型脊髓小脑共济失调（OMIM #615768）的12岁男性患者的人类皮肤成纤维细胞进行了重编程，该患者在STUB1基因中携带复合杂合突变（c.355C>T，c.880A>T）。通过SNP阵列分析和桑格测序证明了无转基因整合和基因组畸变但保留疾病相关突变的诱导多能干细胞系HIHCNi001-A的基因组完整性，同时通过重要多能性标志物的表达以及分化为所有三个胚层细胞的能力验证了其多能性。
