The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues. This atlas captures all major cell classes 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 progenitors to a hierarchical development during the later stages of cell type specification. Both known and unrecorded candidate transcription factors, along with gene regulatory networks that drive the transitions of various cell fates, are identified. Comparisons between the macular and peripheral retinae indicate a largely consistent yet distinct developmental pattern. This atlas 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.
Author affiliation
College of Life Sciences
Psychology & Vision Sciences
Not CurrentPublished in
Nature CommunicationsVolume
15Issue
1Pagination
6792Publisher
Springer Science and Business Media LLCissn
2041-1723eissn
2041-1723Copyright date
2024Available date
2024-09-30Spatial coverage
EnglandLanguage
enDeposited by
Dr Mervyn ThomasDeposit date
2024-08-29Data Access Statement
The RNA-seq and ATAC-seq raw data generated in this study can be accessed at National Center for Biotechnology Information (NCBI) with Sequence Read Archive (SRA) accession ID SRP510712. A copy of raw data has been deposited in the HCA Data Portal - Human Cell Atlas, under accession code 581de139-461f-4875-b408-56453a9082c7 [https://explore.data.humancellatlas.org/projects/581de139-461f-4875-b408-56453a9082c7]. The processed data are available at CZ CELLxGENE Discover with accession code 5900dda8-2dc3-4770-b604084eac1c2c82 [https://cellxgene.cziscience.com/collections/5900dda8-2dc3-4770-b604-084eac1c2c82]. The count matrix for all sequencing data is available at Gene Expression Omnibus, with accession code GSE268630 [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268630]. The binned ATAC-seq peak signaling data used in this study are available in the UCSC Genome Browser Home under session ID HumanDevelopingRetinaAtlas [https://genome.ucsc.edu/s/zhenzuo2/HumanDevelopingRetinaAtlas]. Adult data used for cell major class annotation and cell subclass annotation is provided in Zenodo [https://doi.org/10.5281/zenodo.10806575]. Adult differentially accessible regions, adult histone modification regions, inferred gene regulatory network model, recovered dynamic models, identified differentially expressed genes model, and bigwig files for ATAC are provided in Zenodo [https://doi.org/10.5281/zenodo.10866348]. Source data are provided with this paper as a Source Data file. Source data are provided with this paper.