Table1_Single-Cell RNA-Seq Reveals the Cellular Diversity and Developmental Characteristics of the Retinas of an Infant and a Young Child.XLSX

The human retina, located in the innermost layer of the eye, plays a decisive role in visual perception. Dissecting the heterogeneity of retinal cells is essential for understanding the mechanism of visual development. Here, we performed single-cell RNA-seq to analyze 194,967 cells from the donors of infants and young children, resulting in 17 distinct clusters representing major cell types in the retina: rod photoreceptors (PRs), cone PRs, bipolar cells (BCs), horizontal cells (HCs), amacrine cells (ACs), retinal ganglion cells (RGCs), Müller glial cells (MGs), microglia, and astrocytes (ASTs). Through reclustering, we identified known subtypes of cone PRs as well as additional unreported subpopulations and corresponding markers in BCs. Additionally, we linked inherited retinal diseases (IRDs) to certain cell subtypes or subpopulations through enrichment analysis. We next constructed extensive intercellular communication networks and identified ligand-receptor interactions that play crucial roles in regulating neural cell development and immune homeostasis in the retina. Intriguingly, we found that the status and functions of PRs changed drastically between the young children and adult retina. Overall, our study offers the first retinal cell atlas in infants and young children dissecting the heterogeneity of the retina and identifying the key molecules in the developmental process, which provides an important resource that will pave the way for research on retinal development mechanisms and advancements in regenerative medicine concerning retinal biology.

位于眼球最内层的人类视网膜（human retina）在视觉感知中发挥决定性作用。解析视网膜细胞的异质性，对于理解视觉发育机制至关重要。本研究通过单细胞RNA测序（single-cell RNA-seq）分析了来自婴幼儿供体的194967个细胞，最终得到17个不同的细胞簇，涵盖视网膜主要细胞类型：视杆光感受器细胞（rod photoreceptors, PRs）、视锥光感受器细胞（cone PRs）、双极细胞（bipolar cells, BCs）、水平细胞（horizontal cells, HCs）、无长突细胞（amacrine cells, ACs）、视网膜神经节细胞（retinal ganglion cells, RGCs）、米勒胶质细胞（Müller glial cells, MGs）、小胶质细胞以及星形胶质细胞（astrocytes, ASTs）。通过再聚类分析，本研究不仅鉴定出视锥光感受器细胞的已知亚型，还在双极细胞中发现了此前未被报道的亚群及其对应的标记分子。此外，本研究通过富集分析将遗传性视网膜疾病（inherited retinal diseases, IRDs）与特定细胞亚型或亚群建立关联。随后，本研究构建了大规模的细胞间通讯网络，并鉴定出在调控视网膜神经细胞发育与免疫稳态中发挥关键作用的配体-受体相互作用。值得注意的是，本研究发现视锥光感受器细胞的状态与功能在婴幼儿与成人视网膜之间存在显著差异。综上，本研究首次构建了婴幼儿视网膜细胞图谱，解析了视网膜的细胞异质性并鉴定出发育过程中的关键分子，为视网膜发育机制研究以及视网膜生物学相关再生医学的发展提供了重要的研究资源。