Project description:Molecular specification of cell types underlying central and peripheral vision in primates (macaque peripheral single cell RNA-seq)
Project description: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
Project description: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
Project description:In primates, high-acuity vision is mediated by the fovea, a small specialized central region of the retina. The fovea, unique to the anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, the degree of cellular similarity across anthropoid foveas and the molecular underpinnings of foveal maturation remain unclear. Here, we used high throughput single cell RNA sequencing (scRNA-seq) to profile retinal cells of the common marmoset (Callithrix jacchus), an early divergent in anthropoid evolution from humans, apes, and macaques. We generated atlases of the marmoset fovea and peripheral retina for both neonates and adults.
Project description:The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA-sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ~200 genes, including regulators of cell adhesion and synapse formation. One of these, Igsf9b, a vision-dependent gene encoding an inhibitory synaptic cell adhesion molecule, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell type-specific gene expression programs.
Project description:The retinas of simian primates include a specialized, cone-rich, macula which regards the central visual field and mediates high acuity and colour vision. A prominent feature of the macula is the fovea centralis - a 1 mm-wide, avascular depression in the inner retinal surface that corresponds with a local absence of rods and a peak spatial density of cones in the outer photoreceptor layer. The arrangement of macular photoreceptors, and their specialized ‘midget’ circuits, are the neural substrate for high resolution vision in primates. Macular-specific photoreceptor loss and abnormal blood vessel growth within the macula are the major causes of untreatable vision loss worldwide. However, the genes that regulate specialization of the macula, and the causes of its vulnerability to degeneration, remain obscure. Microarrays were used to compare gene expression between macula and non-macular regions during a critical phase of human retinal vascular development. Keywords: Comparison of developing anatomical regions
Project description:The cornea is the most innervated tissue in the human body. Myelinated axons upon inserting into the peripheral corneal stroma lose their myelin sheaths and continue into the central cornea wrapped by only nonmyelinating corneal SCs (nm-cSCs). This anatomical organization is believed to be important for central vision. Here we employed single-cell RNA sequencing (scRNA-seq), microscopy, and transgenics to characterize these nm-cSCs of the central cornea. Using principal component analysis, uniform manifold approximation and projection, and unsupervised hierarchal cell clustering of scRNA-seq data derived from central corneal cells of male rabbits, we successfully identified several clusters representing different corneal cell types, including a unique cell cluster representing nm-cSCs. To confirm protein expression of cSC genes, we performed cross-species validation, employing corneal whole mount immunostaining with confocal microscopy in mouse corneas. We expect that our results will advance the future study of nm-cSCs in applications of nerve repair, and provide a resource for the study of corneal sensory function.
