Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor.

Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor.
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DOI:
10.1016/j.stem.2012.05.018
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发表时间:
2012-07-06
期刊:
影响因子:
23.9
通讯作者:
Huang, Yadong
Huang, Yadong
中科院分区:
医学1区
文献类型:
--
作者:
Ring, Karen L.;Tong, Leslie M.;Balestra, Maureen E.;Javier, Robyn;Andrews-Zwilling, Yaisa;Li, Gang;Walker, David;Zhang, William R.;Kreitzer, Anatol C.;Huang, Yadong

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从体细胞产生诱导多能干细胞(iPS)和诱导神经元细胞(iN)为神经系统疾病的基础研究和潜在移植疗法提供了新途径。然而,临床应用必须考虑iPS细胞形成肿瘤的风险以及iN细胞在培养中无法自我更新。在这里,我们报告的诱导神经干细胞(iNSCs)的产生从小鼠和人类成纤维细胞直接重编程与一个单一的因素,Sox 2。iNSC表达NSC标记物,并且在其形态、自我更新、形成神经球的能力和基因表达谱方面类似于野生型NSC。克隆的iNSC分化成几种类型的成熟神经元,以及星形胶质细胞和少突胶质细胞,表明多能性。植入的iNSC可以在小鼠脑中存活和整合,并且与iPS细胞衍生的NSC不同,不会产生肿瘤。因此,可以通过重编程直接从成纤维细胞产生不具有致瘤潜力的自我再生和多能iNSC。
The generation of induced pluripotent stem (iPS) cells and induced neuronal (iN) cells from somatic cells provides new avenues for basic research and potential transplantation therapies for neurological diseases. However, clinical applications must consider the risk of tumor formation by iPS cells and the inability of iN cells to self-renew in culture. Here we report the generation of induced neural stem cells (iNSCs) from mouse and human fibroblasts by direct reprogramming with a single factor, Sox2. iNSCs express NSC markers and resemble wild-type NSCs in their morphology, self-renewal, ability to form neurospheres, and gene expression profiles. Cloned iNSCs differentiate into several types of mature neurons, as well as astrocytes and oligodendrocytes, indicating multipotency. Implanted iNSCs can survive and integrate in mouse brains and, unlike iPS cell-derived NSCs, do not generate tumors. Thus, self-renewable and multipotent iNSCs without tumorigenic potential can be generated directly from fibroblasts by reprogramming.
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