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Nat Commun. 2013;4:2373. doi: 10.1038/ncomms3373.

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

Author information

1
Divisions of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
2
Department of Neurosurgery, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.
3
Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
#
Contributed equally

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.

PMID:
23974433
PMCID:
PMC3786770
DOI:
10.1038/ncomms3373
[Indexed for MEDLINE]
Free PMC Article

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