NR2E3 loss disrupts photoreceptor cell maturation and fate in human organoid models of retinal development.

ABSTRACT: While dysfunction and death of light-detecting photoreceptor cells underlie most inherited retinal dystrophies, knowledge of the species-specific details of human rod and cone photoreceptor cell development remains limited. Here, we generated retinal organoids carrying retinal disease-causing variants in NR2E3, as well as isogenic and unrelated controls. Organoids were sampled using single-cell RNA sequencing (scRNA-Seq) across the developmental window encompassing photoreceptor specification, emergence, and maturation. Using scRNA-Seq data, we reconstruct the rod photoreceptor developmental lineage and identify a branch point unique to the disease state. We show that the rod-specific transcription factor NR2E3 is required for the proper expression of genes involved in phototransduction, i

SUBMITTER: Mullin NK 

PROVIDER: S-EPMC11142732 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature