Cell Atlas of the Chick Retina: Single Cell Profiling Identifies 136 Cell Types

Abstract

SUMMARYRetinal structure and function have been studied in many vertebrate orders, but molecular characterization has been largely confined to mammals. We used single-cell RNA sequencing (scRNA-seq) to generate a cell atlas of the chick retina. From ∼40,000 single cell transcriptomes, we identified 136 cell types distributed among the six classes conserved across vertebrates – photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and glial cells. To match molecular profiles to morphology, we adapted a method for CRISPR-based integration of reporters into selectively expressed genes. For Müller glia, we found that transcriptionally distinct cells were regionally localized along the anterior-posterior, dorsal-ventral and central-peripheral retinal axes. We also identified immature photoreceptor, horizontal cell and oligodendrocyte types that persist into late embryonic stages. Finally, we analyzed relationships among chick, mouse and primate retinal cell classes and types. Taken together, our results provide a foundation for anatomical, physiological, evolutionary, and developmental studies of the avian visual system.

Generating and Using Transcriptomically Based Retinal Cell Atlases

“…Until this year (2020), scRNA-seq and snRNA-seq studies of retina focused on mice, macaques, and humans. Recently, however, we and others have begun to assemble atlases of other mammalian species (the marmoset, ferret, pig, and deer mouse; K. Shekhar, W. Yan, J. Hahn, A. Monavarfeshani and J.R. Sanes, unpublished manuscript), as well as two nonmammalian vertebrates, the zebrafish and chick (Hoang et al 2020, Kölsch et al 2021, Yamagata et al 2021. In both the chick and fish, CRISPR-Cas9-based approaches were used to label cell types based on their selective expression of specific genes identified via transcriptomic analysis to match molecularly defined types to morphology.…”

“…Data for zebrafish bipolar cells taken from Y. Kölsch, J. Hahn, K. Shekhar, J.R.Sanes and H. Baier (unpublished manuscript). Data for the chick taken fromYamagata et al (2021). Data for the marmoset and ferret taken from Y. Peng, W. Yan and J.R. Sanes (unpublished manuscript).…”