<b>Single-Cell Atlas of Living and Post-Mortem Human Retina Identifies Specialized Cone States and Cellular Dynamics</b>

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.本研究提供了来自活体捐献者和近期去世个体的人类视网膜样本的高分辨率单细胞RNA测序图谱。通过分析9个视网膜样本中的106,829个细胞，我们生成了视网膜细胞类型比例的综合参考，并识别出特化细胞状态。我们的分析揭示了ELF1-mlCone——一种mlCone光感受器细胞的特化状态，其特征为增强的突触机制（KCNB2、CADPS、RIMS2）和代谢重编程，受关键转录因子ELF1和PRKAA1调控。这一独特状态在独立样本中得到验证，并通过选择性细胞间相互作用整合到视网膜信号网络中。此外，通过比较活体和死后样本，我们的研究揭示了转录动力学的显著差异：活体组织保留了连贯的RNA速度流，可实现准确的伪时间轨迹和动态状态转换，而死后组织则呈现紊乱模式。这些发现强调了活体组织在捕捉活跃细胞状态和转换中的重要性。该图谱整合了细胞类型组成、转录多样性和功能见解，是推进视网膜研究和理解人类视网膜生物学的宝贵资源。