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Inducing different neuronal subtypes from astrocytes in the injured mouse cerebral cortex.
Neuron 103, 1086-1095.e5 (2019)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Aav ; Astrocytes ; Axonal Projection ; Cerebral Cortex ; Cortical Layers ; Electrophysiology ; Inflammation ; Lentivirus ; Reactive Gliosis ; Reprogramming; In-vitro; Brain; Identification; Specification; Deletion; Targets; Cells; Nurr1
Language
english
Publication Year
2019
HGF-reported in Year
2019
ISSN (print) / ISBN
0896-6273
e-ISSN
1097-4199
Journal
Neuron
Quellenangaben
Volume: 103,
Issue: 6,
Pages: 1086-1095.e5
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)
POF-Topic(s)
30204 - Cell Programming and Repair
Research field(s)
Stem Cell and Neuroscience
PSP Element(s)
G-500800-001
WOS ID
WOS:000487763400016
Scopus ID
85072288872
Erfassungsdatum
2019-10-09