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Status |
Public on Jan 07, 2025 |
Title |
AAV-mediated expression of proneural factors stimulates neurogenesis from adult Müller glia in vivo. |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The lack of regeneration in the human central nervous system (CNS) has major health implications. To address this, we previously used transgenic mouse models to show that neurogenesis can be stimulated in the adult mammalian retina by driving regeneration programs that other species activate following injury. Expression of specific proneural factors in adult Müller glia causes them to re-enter the cell cycle and give rise to new neurons following retinal injury. To bring this strategy closer to clinical application, we now show that neurogenesis can also be stimulated when delivering these transcription factors to Müller glia using adeno-associated viral (AAV) vectors. AAV-mediated neurogenesis phenocopies the neurogenesis we observed from transgenic animals, with different proneural factor combinations giving rise to distinct neuronal subtypes in vivo. Vector-borne neurons are morphologically, transcriptomically and physiologically similar to bipolar and amacrine/ganglion-like neurons. These results represent a key step forward in developing a cellular reprogramming approach for regenerative medicine in the CNS.
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Overall design |
Viral vectors expressing proneural genes can reliably stimulate glia of the adult mammalian retina to become various subtypes of neurons.
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Contributor(s) |
Pavlou M, Probst M, Kaplan L, Filippova E, Prieve AR, Rieke F, Reh TA |
Citation missing |
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Submission date |
Jan 06, 2025 |
Last update date |
Jan 08, 2025 |
Contact name |
Thomas Reh |
E-mail(s) |
tomreh@uw.edu
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Organization name |
University of Washington
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Department |
Department of Neurobiology and Biophysics
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Street address |
1959 NE Pacific Street, UW School of Medicine, Seattle, WA 98195
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City |
Seattle |
State/province |
Washington |
ZIP/Postal code |
98195 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (10)
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Relations |
BioProject |
PRJNA1207114 |