title: Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex.
abstract: 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.
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany; INSERM U836, University Grenoble Alpes, Grenoble Institute of Neurosciences, 38000 Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Heinrich
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bergami
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany; Institute for Stem Cell Research, National Research Center for Environment and Health, 85764 Neuherberg, Germany.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gascón
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lepier
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Viganò
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany; Institute for Stem Cell Research, National Research Center for Environment and Health, 85764 Neuherberg, Germany.
authors.forename: Leda
authors.initials: L
authors.lastname: Dimou
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Sutor
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany; Institute of Physiological Chemistry, University Medical Center, Johannes Gutenberg University Mainz, 55128 Mainz, Germany; Focus Program Translational Neuroscience, Johannes Gutenberg University Mainz, 55131 Mainz, Germany. Electronic address: berningb@uni-mainz.de.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Berninger
authors.affiliation: Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, 80336 Munich, Germany; Institute for Stem Cell Research, National Research Center for Environment and Health, 85764 Neuherberg, Germany; Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany. Electronic address: magdalena.goetz@helmholtz-muenchen.de.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D054338:Cell Transdifferentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology* / Q000293:injuries / Q000378:metabolism*; D000089662:Doublecortin Protein; D015870:Gene Expression; D051379:Mice; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055366:Synaptic Potentials / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000089662:Doublecortin Protein; D055748:SOXB1 Transcription Factors; C499317:Ascl1 protein, mouse; C000714847:Dcx protein, mouse