A scRNA-seq Reference Contrasting Living and Early Post-Mortem Human Retina Across Diverse Donor States

This study provides a high-resolution single-cell RNA sequencing atlas of human retinal samples from living donors and recently deceased individuals. By analyzing 106,829 cells from nine retinal samples, we generated a comprehensive reference for retinal cell type proportions and identified specialized cellular states. Our analysis revealed ELF1-mlCone, a specialized state of mlCone photoreceptors characterized by enhanced synaptic machinery (KCNB2, CADPS, RIMS2) and metabolic reprogramming, regulated by key transcription factors ELF1 and PRKAA1. This distinct state was validated across independent samples and was shown to integrate into retinal signaling networks through selective cell-cell interactions. Additionally, by comparing living and post-mortem samples, our study illuminates significant differences in transcriptional dynamics; living tissue preserved coherent RNA velocity streams, enabling accurate pseudotime trajectories and dynamic state transitions, while post-mortem tissue exhibited disorganized patterns. These findings emphasize the importance of living tissue for capturing active cellular states and transitions. This atlas, which integrates cell type composition, transcriptional diversity, and functional insights, represents a valuable resource for advancing retinal research and understanding human retinal biology.