Inducing Different Neuronal Subtypes from Astrocytes in the Injured Mouse Cerebral Cortex

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 elucida...

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Veröffentlicht in:Neuron (Cambridge, Mass.) Jg. 103; H. 6; S. 1086
Hauptverfasser: Mattugini, Nicola, Bocchi, Riccardo, Scheuss, Volker, Russo, Gianluca Luigi, Torper, Olof, Lao, Chu Lan, Götz, Magdalena
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 25.09.2019
Schlagworte:
Animals
Astrocytes - cytology
Astrocytes - metabolism
Basic Helix-Loop-Helix Transcription Factors - genetics
Brain Injuries, Traumatic
Cellular Reprogramming Techniques - methods
Cerebral Cortex - cytology
Cerebral Cortex - injuries
Dependovirus
Genetic Vectors
Gliosis
Gray Matter - cytology
Mice
Nerve Tissue Proteins - genetics
Neurons - cytology
Neurons - metabolism
Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics
Pyramidal Cells - cytology
Pyramidal Cells - metabolism
White Matter - cytology
Wounds, Stab
cortical layers
reprogramming
axonal projection
cerebral cortex
electrophysiology
reactive gliosis
inflammation
AAV
astrocytes
lentivirus
ISSN:1097-4199, 1097-4199
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
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ISSN:1097-4199
1097-4199
DOI:10.1016/j.neuron.2019.08.009