A single-cell guide to retinal development: Cell fate decisions of multipotent retinal progenitors in scRNA-seq

Abstract

Recent advances in high throughput single-cell RNA sequencing (scRNA-seq) technology have enabled the simultaneous transcriptomic profiling of thousands of individual cells in a single experiment. To investigate the intrinsic process of retinal development, researchers have leveraged this technology to quantify gene expression in retinal cells across development, in multiple species, and from numerous important models of human disease. In this review, we summarize recent applications of scRNA-seq and discuss how these datasets have complemented and advanced our understanding of retinal progenitor cell competence, cell fate specification, and differentiation. Finally, we also highlight the outstanding questions in the field that advances in single-cell data generation and analysis will soon be able to answer.

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

“…For each of the three main retinal cell types at this age, we see a cascade of TF motif representation in open chromatin as the cells develop from progenitors to a specific fate. The cascade of motif enrichment we observe for each cell type is consistent with many previously identified TFs known to be important in that cell lineage (Aavani et al, 2017;Shiau et al, 2021;Wu et al, 2021). Overall, there is a good correspondence in the sequence of expression of the most highly expressed TFs by scRNA-seq with the relative abundance of their motifs in accessible chromatin for these cell types (Figure S3A, p < 0.05; Table S3); the Z score of the accessibility in the clusters in a given lineage is significantly correlated with the average RNA expression for each cluster (Figure S3A; Table S3) across the major retinal cell lineages.…”

Comprehensive Characterisation of Fetal and Mature Retinal Cell Identity to Assess the Fidelity of Retinal Organoids

“…After embedding all the single cells into a common space, their visualization on UMAP revealed that the major cell types of the retina clustered together (Figure 4B and S4B). In line with the developmental birth order of retinal neurons and the Müller glial, we observed that fetal samples from up to approximately 100 days of conception contained high proportions of retinal ganglion cells, horizontal cells, and cones (in relation to rod cells) (Figure S4C) (Shiau et al, 2021). Rods, amacrine, bipolar, and Müller cells demonstrated increased proportions after the 100-day time point, in agreement with the knowledge that these cell types are late-born cells.…”

Single-cell RNA-sequencing analysis of the ciliary epithelium and contiguous tissues in the mouse eye

“…This knowledge base will provide the foundation for future studies on ocular pathology and development. Single cell techniques lend themselves to studies of organogenesis ( Haniffa et al, 2021 ) and scRNA-seq has already been successfully deployed to analyze the processes of competence, specification, and differentiation in the developing retina (Shiau et al, 2021) . It is to be expected that the inductive interactions that control the developmental trajectories of cells in the anterior segment will prove similarly amenable to analysis at the single cell level.…”