Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA294311 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2221450.fastq.gz | Fastqsanger.gz | |||
| SRR2221445.fastq.gz | Fastqsanger.gz | |||
| SRR2221446.fastq.gz | Fastqsanger.gz | |||
| SRR2221447.fastq.gz | Fastqsanger.gz | |||
| SRR2221448.fastq.gz | Fastqsanger.gz |
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Project description:Both rod and cone photoreceptors are critical for mammalian vision yet they have important functional differences. In this study, we investigate patterns of DNA methylation and chromatin accessibility in mouse rods and cones. Unexpectedly, we find that a substantial fraction of hypo-methylated regions in the rod methylome are in inaccessible chromatin. These regions show marks of active regulatory regions earlier in neuronal development and could remain undermethylated in adult rods due to their highly compact chromatin. We further identify rod- and cone-enriched regions of accessible chromatin that correspond with cell type-specificity of nearby photoreceptor gene expression. We predict novel DNA signatures of rod and cone specificity and show that NR2E3 function is necessary for rods to gain their complete ensemble of epigenomic features. Taken together, our data capture the epigenomic landscapes of retinal rods and cones, including differences relevant to chromatin structure and photoreceptor biology.
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Project description:The macula of the retina has a high ratio of cones to rods and is critical for central vision and visual acuity. Macula degenerations affect vision the most and are incurable. Here we report the generation, transcriptome profiling, and functional validation of cone-enriched human retinal organoids differentiated from hESCs. Transcriptome profiling using bulk RNA-seq demonstrated that retinal differentiation in vitro recapitulated retinogenesis in vivo in the temporal expression of cell differentiation markers and retinal disease genes, as well as in mRNA alternative splicing. Single-cell RNA-seq of 8-month retinal organoids identified clusters of cone and rod photoreceptors and confirmed the cone enrichment initially revealed by immunostaining. Notably, comparisons of single-cell transcriptomes demonstrated the similarity between retinal organoids and human macula in cones and rods. Cones in retinal organoids exhibited electrophysiological functions. Collectively, we have established cone-enriched retinal organoids and a reference of transcriptomes that are rich resources for retinal studies.
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Project description:Insights into the cellular and molecular evolutionary mechanisms of retinal cells that govern color vision perception across various species are limited. In this study, we established a single-cell prediction (scPred) model to construct an atlas of single-cell retinas from multiple species and subsequently analyzed interspecies variations in the retinal cells of 24 different species. We identified conserved compositions and expression profiles of retinal cells, with photoreceptor cells, including rods, showing dynamic changes from lower to higher species. Moreover, we observed marked interspecies variations in opsin expression patterns and core transcriptional programs that regulate color vision in rods and cones. We also identified distinct cell metabolism patterns and key transcription factors influencing the cell functional difference of different cone types. Notably, our findings indicated an association between fatty acid biosynthesis and OPN1SW+ cones and OPN1MW+ cones, as well as an association between FOXO3 and OPN1LW+ cones across species.
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Project description:Insights into the cellular and molecular evolutionary mechanisms of retinal cells that govern color vision perception across various species are limited. In this study, we established a single-cell prediction (scPred) model to construct an atlas of single-cell retinas from multiple species and subsequently analyzed interspecies variations in the retinal cells of 24 different species. We identified conserved compositions and expression profiles of retinal cells, with photoreceptor cells, including rods, showing dynamic changes from lower to higher species. Moreover, we observed marked interspecies variations in opsin expression patterns and core transcriptional programs that regulate color vision in rods and cones. We also identified distinct cell metabolism patterns and key transcription factors influencing the cell functional difference of different cone types. Notably, our findings indicated an association between fatty acid biosynthesis and OPN1SW+ cones and OPN1MW+ cones, as well as an association between FOXO3 and OPN1LW+ cones across species.
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Project description:Rod photoreceptors are specialized neurons that mediate vision in dim light and are the predominant photoreceptor type in nocturnal mammals. The rods of nocturnal mammals are unique among vertebrate cell types in having an 'inverted' nuclear architecture, with a single dense mass of heterochromatin in the center of the nucleus rather than dispersed clumps at the nuclear periphery. We hypothesized that this unique chromatin organization would correlate with a unique epigenomic landscape as defined by chromatin accessibility. To test this idea, we performed open chromatin profiling (ATAC-seq) on purified mouse rods and their most closely related cell type, cone photoreceptors, which revealed that thousands of loci are selectively closed in rods. Comparison with open-chromatin maps from >60 additional cell types and tissues demonstrated that rods have by far the most closed chromatin architecture. To explore how the unique epigenomic landscape of rods is controlled, we profiled photoreceptors purified from mice lacking the rod master regulator Nrl. We find that the open-chromatin profile of Nrl-/- photoreceptors is nearly indistinguishable from that of native cones, indicating that Nrl is necessary to achieve selective chromatin closure in rods. Finally, we identified distinct enrichments of transcription factor binding sites in rods and cones, suggesting specific mechanisms by which rods and cones encode cell type-specific information in regulatory DNA. Taken together, these data provide new insight into the development and maintenance of photoreceptor identity, and highlight rods as an attractive system for studying the relationship between nuclear organization and local changes in chromatin accessibility.
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2020-10-27 | GSE160138 | GEO
Project description:NRL (Neural retina leucine zipper) is a key regulator of the fate determination and gene expression of rod photoreceptors in the retina of many vertebrates. In this study, we observed a unique retinal phenotype in the nrl knockout zebrafish model characterized by reduced rods with shortened outer segments and gradually increased green-cones in adulthood. By tracing and comparing the developmental processes of WT and nrl knockout rods, we found there might be two waves of rod genesis distinguished as nrl-dependent and independent with different starting times. To reveal the underlying cellular and molecular mechanisms, bulk and single-cell RNA-seq were performed. The changes in gene expression and cell proportion of rods and cones agreed well with our histological and immunofluorescence studies. Interestingly, we found that rods exhibited noticeable heterogeneities in the gene expression patterns, and a part of rods in nrl knockout zebrafish misexpressed the green-cone genes, reflecting a hybrid status of rod and green-cone. Furthermore, we identified mafba as a novel regulator of rod genesis, which was responsible for the development of rods in nrl knockout zebrafish. Our study will largely improve the current understanding of the developmental processes and regulatory mechanisms of rods in zebrafish and probably other species, and may facilitate future studies in the fields of retinal development and retinal degeneration.
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