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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Aav ; Neurogenin2 ; Astrocytes ; Birthdating ; Direct Reprogramming ; Fate Mapping ; Neurons ; Retrovirus ; Viral Vectors; Expression; Cells; Gfap; Transcription; Conversion; Glia; Phosphorylation; Identification; Specificity; Migration
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Zeitschrift Cells
Quellenangaben Band: 13, Heft: 17, Seiten: , Artikelnummer: 408 Supplement: ,
Verlag MDPI
Verlagsort Basel
Institut(e) Institute of Stem Cell Research (ISF)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Stem Cell and Neuroscience
PSP-Element(e) G-500800-001
Förderungen 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
DOI 10.3390/cells13171408
WOS ID 001311272100001
Scopus ID 85203645787
PubMed ID 39272980
Erfassungsdatum 2024-10-24
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