NRL^-/- gene edited human embryonic stem cells generate rod-deficient retinal organoids enriched in S-cone-like photoreceptors.

ABSTRACT: Organoid cultures represent a unique tool to investigate the developmental complexity of tissues like the human retina. NRL is a transcription factor required for the specification and homeostasis of mammalian rod photoreceptors. In Nrl-deficient mice, photoreceptor precursor cells do not differentiate into rods, and instead follow a default photoreceptor specification pathway to generate S-cone-like cells. To investigate whether this genetic switch mechanism is conserved in humans, we used CRISPR/Cas9 gene editing to engineer an NRL-deficient embryonic stem cell (ESC) line (NRL^-/- ), and differentiated it into retinal organoids. Retinal organoids self-organize and resemble embryonic optic vesicles (OVs) that recapitulate the natural histogenesis of rods and cone photoreceptors.

SUBMITTER: Cuevas E 

PROVIDER: S-EPMC8438615 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature