Longitudinal single-cell RNA-seq of hESCs-derived retinal organoids

Human retina development involves multiple well-studied signaling pathways that promote the genesis of a wide arrange of different cell types in a complex architectural structure.Human embryonic stem cells(hESCs)-derived retinal organoids could recapitulate the human retinal development.We performed single-cell RNA-seq of retinal organoids from 5 time points(D36,D66,D96,D126,D186)and identified 9 distinct populations of cells.In addition,we analyzed the molecular characteristics of each main population and followed them from genesis to maturity by pseudotime analysis and characterized the cell-cell interactions between different cell types.Interestingly,we identified insulin receptor(INSR)as a specifically expressed receptor involved in the genesis of photoreceptors,and pleiothropin(PTN)-protein tyrosine phosphatase receptor type Z1(PTPRZ1)as a mediator of a previously unknown interaction between Müller and retinal progenitor cells.Taken together,these findings provide a rich transcriptome-based lineage map for studying human retinal development and modeling developmental disorders in retinal organoids.