Ciliary marginal zone of the developing human retina maintains retinal progenitor cells until late gestational stages

Non-mammalian vertebrates maintain a proliferative cell population at the far periphery of their retina called the ciliary marginal zone (CMZ), which contributes to retinal regeneration upon injury. Humans do not maintain a proliferative CMZ into adulthood; however, it is unknown how long in development this region continues to generate neurons. Here, we identify a population of cells in the far-peripheral retina of the human that continues to proliferate after the rest of the retina is quiescent. Single-cell RNA sequencing and 5-ethynyl-2'-deoxyuridine tracing at late developmental time points reveal that this region has the capacity to produce both early- and late-born cell types late in development and a longer cell cycle than more centrally located retinal progenitor cells (RPCs). Moreover, while most RPCs exit the cell cycle with the addition of a transforming growth factor β inhibitor, early RPCs within the CMZ do not. These findings define the late stages of neurogenesis in human retinal development.