Sep 18, 2019

Epigenetic adaptation prolongs photoreceptor survival during retinal degeneration

BioRxiv : the Preprint Server for Biology
Rachayata DharmatRui Chen


Neural degenerative diseases often display a progressive loss of cells as a stretched exponential distribution. The mechanisms underlying the survival of a subset of genetically identical cells in a population beyond what is expected by chance alone remains unknown. To gain mechanistic insights underlying prolonged cellular survival, we used Spata7 mutant mice as a model and performed single-cell transcriptomic profiling of retinal tissue along the time course of photoreceptor degeneration. Intriguingly, rod cells that survive beyond the initial rapid cell apoptosis phase progressively acquire a distinct transcriptome profile. In these rod cells, expression of photoreceptor-specific phototransduction pathway genes is downregulated while expression of other retinal cell type-specific marker genes is upregulated. These transcriptomic changes are achieved by modulation of the epigenome and changes of the chromatin state at these loci, as indicated by immunofluorescence staining and single-cell ATAC-seq. Consistent with this model, when induction of the repressive epigenetic state is blocked by in vivo histone deacetylase inhibition, all photoreceptors in the mutant retina undergo rapid degeneration, strongly curtailing the stretch...Continue Reading

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Mentioned in this Paper

In Vivo
Inhibition of Histone Deacetylase Activity
Regulation of Biological Process
Nerve Degeneration
Retinal Degeneration
Light Signal Transduction

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