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Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina

By Yi-Rong Peng, Karthik Shekhar, Wenjun Yan, Dustin Herrmann, Anna Sappington, Greg S Bryman, Tavé van Zyl, Michael Tri. H. Do, Aviv Regev, Joshua R. Sanes

Posted 26 Sep 2018
bioRxiv DOI: 10.1101/428110 (published DOI: 10.1016/j.cell.2019.01.004)

High acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible model organisms lack a fovea, its specialized function and dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate and validate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >65 cell types match between the two regions, but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved, but that projection neuron types and programs diverge, despite conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 6 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.

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