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Publication : Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells.

First Author  Jacobi A Year  2022
Journal  Neuron Volume  110
Issue  16 Pages  2625-2645.e7
PubMed ID  35767994 Mgi Jnum  J:329556
Mgi Id  MGI:7332702 Doi  10.1016/j.neuron.2022.06.002
Citation  Jacobi A, et al. (2022) Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells. Neuron 110(16):2625-2645.e7
abstractText  Injured neurons in the adult mammalian central nervous system often die and seldom regenerate axons. To uncover transcriptional pathways that could ameliorate these disappointing responses, we analyzed three interventions that increase survival and regeneration of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC) injury, albeit not to a clinically useful extent. We assessed gene expression in each of 46 RGC types by single-cell transcriptomics following ONC and treatment. We also compared RGCs that regenerated with those that survived but did not regenerate. Each intervention enhanced survival of most RGC types, but type-independent axon regeneration required manipulation of multiple pathways. Distinct computational methods converged on separate sets of genes selectively expressed by RGCs likely to be dying, surviving, or regenerating. Overexpression of genes associated with the regeneration program enhanced both survival and axon regeneration in vivo, indicating that mechanistic analysis can be used to identify novel therapeutic strategies.
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