Direct reprogramming of Sertoli cells into multipotent neural stem cells by defined factors
Direct reprogramming of Sertoli cells into multipotent neural stem cells by defined factors
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通过确定的因素将支持细胞直接重编程为多能神经干细胞
DOI：
10.1038/cr.2011.175
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发表时间：
2012-01-01
期刊：
影响因子：
44.1
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
--
作者：
Sheng, Chao;Zheng, Qinyuan;Zhou, Qi
多能神经干/祖细胞在细胞治疗中具有巨大的前景。将成纤维细胞重编程为诱导多能干细胞以及成熟神经元表明了将终末分化的体细胞转化为多能状态而不首先建立多能性的可能性。在这里，我们证明，来自中胚层的支持细胞可以直接转换成具有神经干/祖细胞特性的多能状态。诱导的神经干/祖细胞（iNSC）表达多种NSC特异性标志物，表现出与正常NSC相似的全局基因表达谱，并且能够自我更新并分化成神经胶质和电生理功能神经元。iNSC衍生的神经元对酪氨酸羟化酶（TH）、γ-氨基丁酸和胆碱乙酰转移酶染色呈阳性。此外，iNSC可以存活并在移植到齿状回后产生突触。iNSC的产生可能对疾病建模和再生医学具有重要意义。
Multipotent neural stem/progenitor cells hold great promise for cell therapy. The reprogramming of fibroblasts to induced pluripotent stem cells as well as mature neurons suggests a possibility to convert a terminally differentiated somatic cell into a multipotent state without first establishing pluripotency. Here, we demonstrate that Sertoli cells derived from mesoderm can be directly converted into a multipotent state that possesses neural stem/progenitor cell properties. The induced neural stem/progenitor cells (iNSCs) express multiple NSC-specific markers, exhibit a global gene-expression profile similar to normal NSCs, and are capable of self-renewal and differentiating into glia and electrophysiologically functional neurons. iNSC-derived neurons stain positive for tyrosine hydroxylase (TH), γ-aminobutyric acid, and choline acetyltransferase. In addition, iNSCs can survive and generate synapses following transplantation into the dentate gyrus. Generation of iNSCs may have important implications for disease modeling and regenerative medicine.