Induction of pluripotent stem cells from autopsy donor-derived somatic cells.
Induction of pluripotent stem cells from autopsy donor-derived somatic cells.
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DOI：
10.1016/j.neulet.2011.07.048
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发表时间：
2011-09-20
影响因子：
2.5
通讯作者：
Craig DW
中科院分区：
文献类型：
--
作者：
Hjelm BE;Rosenberg JB;Szelinger S;Sue LI;Beach TG;Huentelman MJ;Craig DW
人类诱导多能干细胞(IPSCs)已经成为神经疾病建模的一种有趣的方法，因为可以在体外建立保留捐赠者复杂遗传学的神经谱系特定细胞类型。然而，这些基于IPSC的模型的统计能力依赖于对体细胞捐赠者的准确诊断；不幸的是，许多神经退行性疾病在活体受试者中经常被误诊。对捐赠者的大脑进行死后组织病理学检查，结合死前临床标准，往往是正确将个人归类为特定疾病病例或未受影响的对照的最有力的方法。在这项研究中，我们描述了一位75岁男性全身捐赠者的快速尸检中收集的皮肤活检产生的IPSCs，根据临床和组织病理学标准定义为未受影响的神经控制。这些IPSCs是通过慢病毒转导Yamanaka因子、Oct3/4、Sox2、Klf4和c-Myc在无饲养层系统中建立的。经筛选的IPSC克隆同时表达被认为是人胚胎干细胞(HESCs)多能标志的核和表面抗原，并能在体外分化为神经元和神经胶质细胞。统计分析还表明，成纤维细胞的增殖受到活检部位的显著影响，但不影响供者的年龄(在老年队列中)。这些结果证明，尸检供体来源的成纤维细胞可以成功地被重新编程为IPSC，并可能为建立基于IPSC的神经疾病模型提供一种有利的方法。
Human induced pluripotent stem cells (iPSCs) have become an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. In this study, we describe iPSCs generated from a skin biopsy collected postmortem during the rapid autopsy of a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. These iPSCs were established in a feeder-free system by lentiviral transduction of the Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. Selected iPSC clones expressed both nuclear and surface antigens recognized as pluripotency markers of human embryonic stem cells (hESCs) and were able to differentiate in vitro into neurons and glia. Statistical analysis also demonstrated that fibroblast proliferation was significantly affected by biopsy site, but not donor age (within an elderly cohort). These results provide evidence that autopsy donor-derived fibroblasts can be successfully reprogrammed into iPSCs, and may provide an advantageous approach for generating iPSC-based neurological disease models.
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