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

Abstract

AbstractBackgroundThe retina plays a vital role in capturing and processing visual information in vertebrates, allowing them to adapt to diverse environments. Single-cell expression profiles of the vertebrate retina have been described; however, a deeper understanding of the expression patterns in the context of development and evolution among homologous cell types is lacking. To identify such shared patterns, we examined and compared approximately 230,000 retinal cells from three species: mouse, chicken, and zebrafish.ResultsWe 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 with 381 regulators across the three species. In addition, we identified 10 common cell type-specific regulators and 16 preserved regulons. Using RNA velocity analysis, we pinpointed conserved driver genes key to retinal cell differentiation in both mouse and zebrafish, and by intersecting regulators, we extracted the crucial regulators that facilitate these differentiation processes. Finally, investigation of the potential origins of photoreceptors and retinal ganglion cells by examining conserved expression patterns among the three vertebrate species and the invertebrateCiona intestinalisrevealed functional similarities in light transduction mechanisms betweenCionaphotoreceptor-related cells and vertebrate retinal cells.ConclusionsOur findings offer insights into the conserved regulatory frameworks intrinsic, evolutionarily preserved differentiation programs, and ancestral origins of vertebrate retinal cells.