Human retinal organoid single-cell atlas allows to reconstruct retinal development at high resolution and identify nature restricted transcriptional states in vitro

The vertebrate retina is a specialized neural tissue essential for capturing and processing visual information, and disruptions in its development can lead to blindness. Human pluripotent stem cell–derived retinal organoids model many aspects of retinal morphogenesis, yet their complexity, dynamic cell state transitions, and unique in vitro–specific populations present challenges for assessing developmental fidelity and therapeutic potential. We present the Human Retinal Organoid Cell Atlas (HROCA), a single-cell transcriptomic reference spanning Day 10 to Day 365 of organoid development, integrating 458,309 cells from 15 studies. By comparing HROCA with the human fetal retina atlas, we identify protocol-specific differences, neuronal maturation limits, and timing discrepancies, as well as consistent populations of chimeric, non-canonical, and apatride cells absent from classical retinal taxonomy. This resource advances understanding of retinal development, benchmarks organoid models, and informs strategies for regenerative medicine.