Comprehensive Characterisation of Fetal and Mature Retinal Cell Identity to Assess the Fidelity of Retinal Organoids

Abstract: Characterizing cell identity in complex tissues such as the human retina is essential for studying its development and disease. While retinal organoids derived from pluripotent stem cells have been widely used to model development and disease of the human retina, there is a lack of studies that have systematically evaluated molecular and cellular fidelity of the organoids derived from various culture protocols in recapitulating their in vivo counterpart. 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 our retinal cell identity map from the fetal and adult tissues, 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.