期刊
BRAIN RESEARCH
卷 1615, 期 -, 页码 51-60出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2015.04.027
关键词
Neurogenin 2; Reprogramming; Induced neuron
资金
- Nanjing Medical Science and Technique Development Foundation
- Nanjing Department of Health [ZKX13035, QRX11197]
- National Natural Science Foundation of China [81171147, 81271003]
- Xingwei Project Key Personal Medical Research Foundation of Health Department of Jiangsu Province [RC201156]
- Six Categories of Key Person Research Foundation of Jiangsu Province [069]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [JX10231801]
Direct lineage reprogramming of human fibroblasts into functional neurons holds great promise for biomedical applications such as regenerative medicine and cellbased disease modelling. However, clinical applications must consider how to increase neuronal conversion efficiency and at the same time reduce the number of required transcription factors. Here, we investigated whether Neurogenin 2 (Ngn2), which is a proneural gene that directs neuronal differentiation of progenitor cells during development, can enhance the generation of patient-specific induced neuronal cells. In this study, we transfected Ascl1., Sox2 and Ngn2 into human fibroblasts from the patients' scalp by lentivirus. Morphological analysis, immunocytochemistry, gene expression and electrophysiological analysis were performed to identify the similarity of induced neuronal cells (iNCs) to human neuronal cells. Ngn2 increase the conversion efficiency from 4% to 13.4%. iNCs express neuronal cell markers and resemble wild-type neurons in their morphology, gene expression profiles and exhibit functional membrane properties of mature neurons. Implanted iNCs can survive and integrate in mouse brains and, unlike iPS cell-derived neural cells, do not generate tumours. (C) 2015 Elsevier B.V. All rights reserved.
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