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Puglisi, M. ; Lao, C.L. ; Wani, G. ; Masserdotti, G. ; Bocchi, R. ; Götz, M.

Comparing viral vectors and fate mapping approaches for astrocyte-to-neuron reprogramming in the injured mouse cerebral cortex.

Cells 13:408 (2024)

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	Open Access Gold

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Direct neuronal reprogramming is a promising approach to replace neurons lost due to disease via the conversion of endogenous glia reacting to brain injury into neurons. However, it is essential to demonstrate that the newly generated neurons originate from glial cells and/or show that they are not pre-existing endogenous neurons. Here, we use controls for both requirements while comparing two viral vector systems (Mo-MLVs and AAVs) for the expression of the same neurogenic factor, the phosphorylation-resistant form of Neurogenin2. Our results show that Mo-MLVs targeting proliferating glial cells after traumatic brain injury reliably convert astrocytes into neurons, as assessed by genetic fate mapping of astrocytes. Conversely, expressing the same neurogenic factor in a flexed AAV system results in artefactual labelling of endogenous neurons fatemapped by birthdating in development that are negative for the genetic fate mapping marker induced in astrocytes. These results are further corroborated by chronic live in vivo imaging. Taken together, the phosphorylation-resistant form of Neurogenin2 is more efficient in reprogramming reactive glia into neurons than its wildtype counterpart in vivo using retroviral vectors (Mo-MLVs) targeting proliferating glia. Conversely, AAV-mediated expression generates artefacts and is not sufficient to achieve fate conversion.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Aav ; Neurogenin2 ; Astrocytes ; Birthdating ; Direct Reprogramming ; Fate Mapping ; Neurons ; Retrovirus ; Viral Vectors; Expression; Cells; Gfap; Transcription; Conversion; Glia; Phosphorylation; Identification; Specificity; Migration

ISSN (print) / ISBN 2073-4409

e-ISSN 2073-4409

Journal Cells

Quellenangaben Volume: 13, Issue: 17, Article Number: 408

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Institute(s) Institute of Stem Cell Research (ISF)

Grants European Union
SyNergy
EU (NSC-Reconstruct, H2020)
Frontiers in Research Fund Transformation grant funded through Canadian Institutes of Health Research
Frontiers in Research Fund Transformation grant funded through Natural Sciences and Engineering Research Council of Canada and Social Sciences
Frontiers in Research Fund Transformation grant funded through Humanities Research Council of Canada
German Research Foundation