Single-cell ATAC-seq of fetal human retina and stem-cell-derived retinal organoids shows changing chromatin landscapes during cell fate acquisition

We previously used single-cell transcriptomic analysis to characterize human fetal retinal development and assessed the degree to which retinal organoids recapitulate normal development. We now extend the transcriptomic analyses to incorporate single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), a powerful method used to characterize potential gene regulatory networks through the changes in accessible chromatin that accompany cell-state changes. The combination of scATAC-seq and single-cell RNA sequencing (scRNA-seq) provides a view of developing human retina at an unprecedented resolution. We identify key transcription factors relevant to specific fates and the order of the transcription factor cascades that define each of the major retinal cell types. The changing chromatin landscape is largely recapitulated in retinal organoids; however, there are differences in Notch signaling and amacrine cell gene regulation. The datasets we generated constitute an excellent resource for the continued improvement of retinal organoid technology and have the potential to inform and accelerate regenerative medicine approaches to retinal diseases.

Automated summary

This study combines single-cell transcriptomic analysis with chromatin sequencing to investigate human fetal retinal development and identify key transcription factors and their cascades. By comparing retinal organoids, differences in signaling pathways and gene regulation are discovered. These findings are crucial for improving retinal organoid technology and advancing regenerative medicine approaches for retinal diseases.