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Inducing Different Neuronal Subtypes from Astrocytes in the Injured Mouse Cerebral Cortex
Open accessAbstract
Astrocytes are particularly promising candidates for reprogramming into neurons, as they maintain some of the original patterning information from their radial glial ancestors. However, to which extent the position of astrocytes influences the fate of reprogrammed neurons remains unknown. To elucidate this, we performed stab wound injury covering an entire neocortical column, including the gray matter (GM) and white matter (WM), and targeted local reactive astrocytes via injecting FLEx switch (Cre-On) adeno-associated viral (AAV) vectors into mGFAP-Cre mice. Single proneural factors were not sufficient for adequate reprogramming, although their combination with the nuclear receptor-related 1 protein (Nurr1) improved reprogramming efficiency. Nurr1 and Neurogenin 2 (Ngn2) resulted in high-efficiency reprogramming of targeted astrocytes into neurons that develop lamina-specific hallmarks, including the appropriate long-distance axonal projections. Surprisingly, in the WM, we did not observe any reprogrammed neurons, thereby unveiling a crucial role of region- and layer-specific differences in astrocyte reprogramming.
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“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 [10]
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Metadata
- Authors
- Mattugini, N., Bocchi, R., Scheuss, V., Russo, G. L., Torper, O., Lao, C. L., & Götz, M.
- Affiliations
- Helmholtz Munich (DE)
- Corresponding author
- Götz, Magdalena
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 103
- Issue
- 6
- Pages
- 1086-1095.e5
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC6859713
- OpenAlex
- W2971841027
- Cited by
- 159
- References
- 42
- Citations by year
- 2026: 12 · 2025: 26 · 2024: 28 · 2023: 19 · 2022: 26 · 2021: 35 · 2020: 11 · 2019: 2
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc-nd)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P400PB_183826, P2GEP3_174900)
- European Research Council (340793)
- Fondation Roger de Spoelberch
- ERA-LEARN 2020
- Deutsche Forschungsgemeinschaft (01EW1705B, SFB 870, A06)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- neuronal subtype specification, stab wounds, cerebral cortex, Nurr1, Neurogenin2, white matter, gray matter, adeno-associated virus vectors
- MeSH terms
- Cellular Reprogramming Techniques, Brain Injuries, Traumatic, Dependovirus, Animals, Astrocytes, Cerebral Cortex, Genetic Vectors, Gliosis, Nerve Tissue Proteins, Neurons, Wounds, Stab, Pyramidal Cells, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Nuclear Receptor Subfamily 4, Group A, Member 2, White Matter, Gray Matter
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