Divisions of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Department of Neurosurgery, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.
Nat Commun. 2013;4:2373. doi: 10.1038/ncomms3373.
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 the 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 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 Neurogenin2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischaemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo.
将非神经细胞直接重编程为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还知之甚少。在这里，我们表明，区域差异和损伤条件对成年啮齿动物大脑中重编程的效果以及新生成神经元的后续存活有显著影响。局部暴露于生长因子和逆转录病毒介导的神经发生转录因子 Neurogenin2 的过表达的组合可以诱导成年新皮质和纹状体中非神经元细胞产生新的神经元，而这些区域中的神经元更替非常有限。这两个区域对生长因子和 Neurogenin2 的反应不同，并指示新神经元表现出不同的分子表型。此外，缺血性损伤对这些区域中新神经元的分化有不同的影响。这些结果表明，体内直接神经元重编程受到强烈的环境影响。
