Comparative single-cell transcriptomic analysis reveals key differentiation drivers and potential origin of vertebrate retina

Despite known single-cell expression profiles in vertebrate retinas, understanding of their developmental and evolutionary expression patterns among homologous cell types remains limited. We examined and compared approximately 230,000 retinal cells from three species and found significant similarities among homologous cell types, indicating inherent regulatory patterns. To understand these shared patterns, we constructed gene regulatory networks for each developmental stage for the three species. We identified 690 regulons governed by 530 regulators across three species, along with 10 common cell type-specific regulators and 16 preserved regulons. RNA velocity analysis pinpointed conserved driver genes and regulators key to retinal cell differentiation in both mouse and zebrafish. Investigation of the origins of retinal cells by examining conserved expression patterns between vertebrate retinal cells and invertebrate Ciona intestinalis photoreceptor-related cells revealed functional similarities in light transduction mechanisms. Our findings offer insights into the evolutionarily conserved regulatory frameworks and differentiation drivers of vertebrate retinal cells. ### Competing Interest Statement The authors have declared no competing interest.