Single Cell Multiome Atlas of the Human Developing Retina

The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generated a single-nuclei multi-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 donors aged between 8 and 23 weeks post-conception with matched macular and peripheral tissues from each donor. This atlas captures all major cell classes and over 60 cell types in the retina along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitor cells to a hierarchical development during the later stages of cell type specification. Both known and novel candidate transcription factors, along with gene regulatory networks that drive the transitions of various cell fates, are identified. Comparisons between the macular and peripheral retina indicate a largely consistent yet distinct developmental pattern. Furthermore, the retinoic acid pathway emerges as a potential key driver for retinal patterning. This multi-omic atlas of the developing retina offers unparalleled resolution into the transcriptional and chromatin accessibility landscapes during development, providing an invaluable resource for deeper insights into retinal development and associated diseases.