In vivo reprogramming of astrocytes to neuroblasts in the adult brain.
In vivo reprogramming of astrocytes to neuroblasts in the adult brain.
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DOI：
10.1038/ncb2843
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发表时间：
2013-10
影响因子：
21.3
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中科院分区：
文献类型：
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成体分化的细胞可以在培养中重新编程为多能干细胞或谱系受限的增殖前体细胞；然而，这一点尚未在体内得到证实。在这里，我们证明了单个转录因子SOX2足以将成年小鼠大脑中的常驻星形胶质细胞重新编程为增殖的神经母细胞。这些诱导的成人神经母细胞(IANB)持续数月，即使在老化的大脑中也能产生。当给予BDNF和noggin或用组蛋白去乙酰酶抑制剂治疗小鼠时，iANB会发育成电生理成熟的神经元，并在功能上整合到局部神经网络中。我们的结果表明，成体星形胶质细胞在体内表现出显著的可塑性，这一特征可能对使用内源性患者特有的神经胶质细胞再生中枢神经系统具有重要意义。
Adult differentiated cells can be reprogrammed into pluripotent stem cells or lineage-restricted proliferating precursors in culture; however, this has not been demonstrated in vivo. Here, we show that the single transcription factor SOX2 is sufficient to reprogram resident astrocytes into proliferative neuroblasts in the adult mouse brain. These induced adult neuroblasts (iANBs) persist for months and can be generated even in aged brains. When supplied with BDNF and noggin or when the mice are treated with a histone deacetylase inhibitor, iANBs develop into electrophysiologically mature neurons, which functionally integrate into the local neural network. Our results demonstrate that adult astrocytes exhibit remarkable plasticity in vivo, a feature that might have important implications in regeneration of the central nervous system using endogenous patient-specific glial cells.