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Status |
Public on Jun 25, 2017 |
Title |
Sox11 expression in adult retina promotes regeneration of some ganglion cell types but kills others |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
At least 30 types of retinal ganglion cell (RGC) send distinct messages through the optic nerve to the brain. Strategies for promoting regeneration of RGC axons following injury act on only some of these types. Here we tested the hypothesis that over-expressing developmentally important transcription factors in adult RGCs could reprogram them to a “youthful” growth-competent state and promote regeneration of other types. From a screen of transcription factors expressed by developing RGCs, we found one, Sox11, that induced substantial axon regeneration. Transcriptome profiling confirmed that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, alpha-RGCs, which preferentially regenerate following treatments such as PTEN deletion, were killed by Sox 11. Thus, Sox 11 promotes regeneration of non-alpha RGCs, which are refractory to PTEN. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state and that different growth-promoting interventions act on distinct neuronal types.
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Overall design |
We compared transcriptomes of retinal ganglion cells between AAV-Control retinas, and retinas treated with AAV-Sox11 overexpression. We then performed optic nerve crush, and 3 days later purified RGCs using FACS. RGCs were marked with Thy1-PE-Cy7 antibody and with live/dead cell staining. We performed sample preparations in full triplicate, and in each replicate we always performed Control and Sox11 on the same day, in alternating order.
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Contributor(s) |
Norsworthy M, Bei F, Kawaguchi R, Wang C, Wang Q, Brommer B, Sanes J, Coppola G, He Z |
Citation(s) |
28641110 |
Submission date |
Sep 17, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Riki Kawaguchi |
E-mail(s) |
rkawaguchi@mednet.ucla.edu
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Phone |
4244424783
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Organization name |
University of California Los Angeles
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Department |
Department of Neurology and Department of Psychiatry
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Lab |
Informatics Center for Neurogenetics and Neurogenomics (ICNN).
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Street address |
760 Westwood Plaza, Room 37-420
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City |
Los Angeles |
State/province |
CA |
ZIP/Postal code |
90095-1759 |
Country |
USA |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA343308 |
SRA |
SRP090059 |