Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex

TY - JOUR

T1 - Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex

AU - Heinrich, Christophe

AU - Bergami, Matteo

AU - Gascón, Sergio

AU - Lepier, Alexandra

AU - Viganò, Francesca

AU - Dimou, Leda

AU - Sutor, Bernd

AU - Berninger, Benedikt

AU - Götz, Magdalena

PY - 2014/12/9

Y1 - 2014/12/9

N2 - The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX)+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.

AB - The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX)+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.

UR - http://www.scopus.com/inward/record.url?scp=84922642870&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2014.10.007

DO - 10.1016/j.stemcr.2014.10.007

M3 - Article

C2 - 25458895

AN - SCOPUS:84922642870

SN - 2213-6711

VL - 3

SP - 1000

EP - 1014

JO - Stem cell reports

JF - Stem cell reports

IS - 6

ER -