期刊
NEUROSCIENCE LETTERS
卷 502, 期 3, 页码 219-224出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.07.048
关键词
Induced pluripotent stem cells; Genetic disease models; Diagnostics; Neurodegenerative diseases; Postmortem; Autopsy; Neural differentiation
资金
- National Institute of Neurological Disorders and Stroke [NINDS, 5U24NS051872-05, NINDS, R01NS05987]
- Arizona Alzheimer's Consortium
- National Institute on Aging, Arizona Alzheimer's Disease Core Center [P30 AG19610]
- Stardust Foundation
- Marley Foundation
- Arizona Department of Health Services, Arizona Alzheimer's Research Center [211002]
- Arizona Biomedical Research Commission, Arizona Parkinson's Disease Consortium [4001, 0011, 05-901]
- Michael J. Fox Foundation for Parkinson's Research
- State of Arizona
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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据