Single-cell nuclear transcriptome sequencing and cross-species analysis reveal tree shrew retina Age-associated cellular profiles and specific markers
Tree shrews (TS) possess a highly developed visual system with great potential for modelling human age-related diseases in eyes. However, the cellular and molecular characteristics of the TS retina are rarely understood. Here, we used single-nucleus RNA sequencing (snRNA-seq) to analyze the cellular map of the TS retina and determine the involvement of each cell type in retinal development during the postnatal lifespan. Intriguingly, increases in cones and retinal ganglion cells (RGCs), along with a reduction in rods and bipolar cells, were observed in the TS retina with an increase in age. Moreover, differential gene expression and histological analysis revealed retinal cell type-specific crucial genes in the developmental progression of TS. Especially, we observed that the circadian rhythm increased with age in TS from young to adult and elder stage, reflected in an increase in cone and RGC cells. Meanwhile, age-related TS-specific intercellular interactions in the retina were depicted, and these complex cell-cell communications may contribute to retinal degradation resistance and retinal homeostasis. Importantly, cross-species analysis compared the differences in retinal cell types and gene expression among TS, chicks, mice, primate macaques, and humans. TS exhibited a similar overall transcriptome expression associated with that in mice, which may be attributed to the higher complexity of retinal cell subtypes. Our findings for the first time decipher the cellular and molecular signatures in TS retina in different developmental stages, providing insights into the potential of TS as suitable animal model for studying retinal senescence and related disorders. Overall design: We used single-nucleus RNA sequencing (snRNA-seq) to analyze the cellular map of the TS retina and determine the involvement of each cell type in retinal development during the postnatal lifespan.