Environmental impact on direct neuronal reprogramming in vivo in the adult brain.

Environmental impact on direct neuronal reprogramming in vivo in the adult brain.
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DOI:
10.1038/ncomms3373
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发表时间:
2013
影响因子:
16.6
通讯作者:
Nakafuku, Masato
Nakafuku, Masato
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Grande, Andrew;Sumiyoshi, Kyoko;Lopez-Juarez, Alejandro;Howard, Jennifer;Sakthivel, Bhuvaneswari;Aronow, Bruce;Campbell, Kenneth;Nakafuku, Masato

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直接重编程非神经元细胞以产生新的神经元是修复受损大脑的一种很有前途的方法。然而,体内环境对神经元重编程的影响尚不清楚。本研究表明,区域差异和损伤条件对成年啮齿动物大脑新生神经元的重编程效果和随后的存活有显著影响。局部暴露于生长因子和逆转录病毒介导的神经源性转录因子Neurogenin2 (Neurog2)的过表达可以诱导成人新皮层和纹状体中的非神经元细胞产生新的神经元,否则神经元的更新非常有限。这两个区域对生长因子和Neurog2的反应不同,并指导新神经元表现出不同的分子表型。此外,缺血损伤对这些区域新神经元分化的影响也存在差异。这些结果证明了环境对体内神经元重编程的直接影响。
Direct reprogramming of non-neuronal cells to generate new neurons is a promising approach to repair damaged brains. Impact of the in vivo environment on neuronal reprogramming, however, is poorly understood. Here we show that regional differences and injury conditions have significant influence on the efficacy of reprogramming and subsequent survival of newly generated neurons in the adult rodent brain. A combination of local exposure to growth factors and retrovirus-mediated overexpression of the neurogenic transcription factor Neurogenin2 (Neurog2) can induce new neurons from non-neuronal cells in the adult neocortex and striatum where neuronal turnover is otherwise very limited. These two regions respond to growth factors and Neurog2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo.
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