Unraveling the developmental heterogeneity of human retinal ganglion cells within the developing retina to study to the continuity of maturation

We assembled a single-cell RNA-seq atlas of the human fetal retina spanning weeks 8–27 to investigate the continuous maturation of retinal ganglion cells (RGCs). Assuming that RGC maturation is a gradual rather than discrete process, we applied pseudotime analysis to align RGC transcriptomes within the broader developmental timeline, revealing a continuous maturation track. This framework allowed us to define cell-intrinsic features (differentially expressed genes, maturation profiles, regulons, transcriptional motifs) and cell-extrinsic features (neurotrophic receptor expression, cell–cell interactions) associated with distinct maturation states, including novel RGC maturation drivers. We also demonstrated the utility of this atlas as a reference for automated annotation and universal embedding of scRNA-seq datasets. Our results add a maturation dimension to retinal cell class–state analysis and provide a transcriptomic roadmap for developmental studies of the retina.