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Molecular specification of cell types underlying central and peripheral vision in primates (macaque peripheral single cell RNA-seq)

ABSTRACT: Among mammals, only primates including human possess a small central retinal region called the fovea, which mediates high acuity vision. As other mammals lack a fovea, molecular bases of its specialized function and dysfunction in retinal diseases remain poorly understood. By analyzing >165,000 single-cell transcriptomes from macaque fovea and peripheral retina, we identified and molecularly characterized >60 major cell types in each region. A few cell types are unique to each region, and there are also substantial differences in proportions and gene expression between corresponding types in the two areas, some of which can be related to functional differences. Comparison of macaque and mouse retinal taxonomies reveals both similarities and differences between species. Many molecular features of macaque retinal cell types are conserved in two other primates, marmosets and humans, and key human retinal disease-associated genes are expressed in specific macaque cell types

ORGANISM(S): Macaca fascicularis

PROVIDER: GSE118852 | GEO | 2019/02/06

REPOSITORIES: GEO

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Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness. DNA methylome analysis of pooled Human, Chimpanzee and Macaque

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Molecular specification of cell types underlying central and peripheral vision in primates (macaque peripheral single cell RNA-seq)

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