Generation of primitive neural stem cells from human fibroblasts using a defined set of factors.
Generation of primitive neural stem cells from human fibroblasts using a defined set of factors.
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DOI：
10.1242/bio.013151
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发表时间：
2015-10-21
期刊：
影响因子：
2.4
通讯作者：
Akutsu H
中科院分区：
文献类型：
--
作者：
Miura T;Sugawara T;Fukuda A;Tamoto R;Kawasaki T;Umezawa A;Akutsu H
在小鼠中，依赖于白血病抑制因子(LIF)的原始神经干细胞(NSCs)比依赖于bFGF的确定性NSCs具有更高的神经分化潜能。因此，研究和开发神经疾病的治疗策略需要可扩展的原始神经干细胞。目前还缺乏合适的技术来产生人类长期可扩增的原始神经干细胞。在这里，我们描述了一种利用基于诱导多能干细胞(IPSCs)生成技术的策略将人成纤维细胞转化为LIF依赖的原始神经干细胞的方法。这些LIF依赖的诱导神经干细胞(LD-iNSCs)可以扩增至100代。长期培养的LD-iNSCs显示出多潜能的神经分化潜能，可以产生运动神经元和多巴胺能神经元，以及星形胶质细胞和少突胶质细胞，显示出高度的可塑性。此外，LD-iNSCs很容易恢复为人类IPSC，表明LD-iNSCs处于中间IPSC状态。这种方法可能有助于产生患者特有的人类神经元，用于研究和治疗神经退行性疾病。摘要：一种新的方法可以从人成纤维细胞中产生自我更新、多潜能和神经谱系受限的LIF依赖的诱导原始神经干细胞(LD-iNSCs)，为人类神经细胞的研究奠定了基础。
In mice, leukemia inhibitory factor (LIF)-dependent primitive neural stem cells (NSCs) have a higher neurogenic potential than bFGF-dependent definitive NSCs. Therefore, expandable primitive NSCs are required for research and for the development of therapeutic strategies for neurological diseases. There is a dearth of suitable techniques for the generation of human long-term expandable primitive NSCs. Here, we have described a method for the conversion of human fibroblasts to LIF-dependent primitive NSCs using a strategy based on techniques for the generation of induced pluripotent stem cells (iPSCs). These LIF-dependent induced NSCs (LD-iNSCs) can be expanded for >100 passages. Long-term cultured LD-iNSCs demonstrated multipotent neural differentiation potential and could generate motor neurons and dopaminergic neurons, as well as astrocytes and oligodendrocytes, indicating a high level of plasticity. Furthermore, LD-iNSCs easily reverted to human iPSCs, indicating that LD-iNSCs are in an intermediate iPSC state. This method may facilitate the generation of patient-specific human neurons for studies and treatment of neurodegenerative diseases. Summary: A novel method for the generation of self-renewable, multipotent and neural lineage-restricted LIF-dependent induced primitive neural stem cells (LD-iNSCs) from human fibroblasts with the potential to facilitate human neuronal studies.