Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex
Open accessAbstract
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.
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Astrocyte-to-neuron reprogramming has recently emerged as an appealing regenerative strategy because astrocytes represent an endogenous cellular reservoir from which new neurons might be generated in situ.
“Astrocyte-to-neuron reprogramming has recently emerged as an appealing regenerative strategy because astrocytes, which are abundant, regionally distributed, and proliferative, represent an endogenous cellular reservoir from which new neurons might be generated in situ.”
From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [11]
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- Authors
- Heinrich, C., Bergami, M., Gascón, S., Lepier, A., Viganò, F., Dimou, L., Sutor, B., Berninger, B., & Götz, M.
- Affiliations
- Inserm (FR)
- Physiologisches Institut (DE)
- Johannes Gutenberg University Mainz (DE)
- Munich Cluster for Systems Neurology (DE)
- Corresponding author
- Berninger, Benedikt
- Götz, Magdalena
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 3
- Issue
- 6
- Pages
- 1000-1014
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4264057
- OpenAlex
- W2017830127
- Cited by
- 323
- References
- 39
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 30 · 2023: 20 · 2022: 23 · 2021: 29 · 2020: 22 · 2019: 29 · 2018: 31 · 2017: 40 · 2016: 27 · 2015: 36 · 2014: 2
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- SOX2, NG2 glia, induced neurons, ASCL1, doublecortin, cerebral cortex injury, traumatic brain injury, retroviral gene transfer, neuronal reprogramming, synaptic integration
- MeSH terms
- Doublecortin Protein, Animals, Cerebral Cortex, Neuroglia, Neurons, Gene Expression, Cell Proliferation, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Cell Transdifferentiation, Synaptic Potentials, SOXB1 Transcription Factors, Cellular Reprogramming
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