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Series GSE136880 Query DataSets for GSE136880
Status Public on Jun 02, 2020
Title Epigenetic adaptation prolongs photoreceptor survival during retinal degeneration
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Neural degenerative diseases often display a progressive loss of cells at as a stretched exponential ratedistribution. The mechanisms underlying the survival of a subset of clonal 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 direct modulation of the epigenomeetic modifications and changes of the chromatin state at these gene loci, as indicated by immunofluorescence staining and single-cell ATAC-seq. Consistent with this model, when the induction of the repressive epigenetic state is blocked by in vivo histone deacetylase HDAC inhibition, all photoreceptors in the mutant retina undergo rapid degeneration, strongly curtailing the stretched exponential distribution. Altogether, oOur study reveals an intrinsic mechanism by which the neuralon cells progressively adapt to the genetic stress to achieve prolonged survival through epigenomic regulation and chromatin state modulation.
Overall design To globally characterize the of retinal tissue along the time course of photoreceptor degeneration, we performed single cell RNA sequencing of retinal cells from wild type and Spata7 knockout mutant mice at 1, 3, 6 month. we used Spata7 mutant mice as a model. To globally characterize the of retinal tissue along the time course of photoreceptor degeneration, we performed single cell ATAC sequencing of retinal cells from 7M wild type and 6M Spata7 knockout mutant mice.
Contributor(s) Dharmat R, Li Y, Chen R
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Submission date Sep 04, 2019
Last update date Jun 07, 2020
Contact name sangbae Kim
Organization name Baylor College of Medicine
Street address 1 baylor plaza
City Houston
ZIP/Postal code 77030
Country USA
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM4060292 Spata7_WT_1M
GSM4060293 Spata7_WT_3M
GSM4060294 Spata7_WT_6M
BioProject PRJNA563908
SRA SRP220355

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Supplementary file Size Download File type/resource
GSE136880_RAW.tar 123.8 Mb (http)(custom) TAR (of H5, TSV, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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