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

Andrew Grande, Kyoko Sumiyoshi, Alejandro López-Juárez, Jennifer Howard, Bhuvaneswari Sakthivel, Bruce Aronow, Kenneth Campbell and Masato Nakafuku ()
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Andrew Grande: Cincinnati Children’s Hospital Research Foundation
Kyoko Sumiyoshi: Cincinnati Children’s Hospital Research Foundation
Alejandro López-Juárez: Cincinnati Children’s Hospital Research Foundation
Jennifer Howard: Cincinnati Children’s Hospital Research Foundation
Bhuvaneswari Sakthivel: Cincinnati Children’s Hospital Research Foundation
Bruce Aronow: Cincinnati Children’s Hospital Research Foundation
Kenneth Campbell: Cincinnati Children’s Hospital Research Foundation
Masato Nakafuku: Cincinnati Children’s Hospital Research Foundation

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms3373

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