A comprehensive characterisation of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

Retinal organoids derived from pluripotent stem cells have been widely used to model development and disease of the human eye. Yet there is a lack of studies that have systematically evaluated the fidelity of the organoids to their in vivo counterpart. This is particularly relevant for evaluating the efficacy of therapeutic applications and culture protocol performance. To this end, we performed an extensive meta-atlas characterisation of cellular identities of the human eye, covering a wide range of developmental stages. The resulting map uncovered previously unknown biomarkers of major retinal cell types and those associated with cell-type specific maturation. Using these retinal identities from fetal and adult tissue as the map, we systematically assessed the fidelity of the retinal organoids to mimic the human eye, enabling us to comprehensively benchmark the current protocols for retinal organoid generation. Overall design: Single-cell RNA sequencing of 3-month-old retinal organoids