Single-Cell RNA-Seq Reveals Conserved Cellular Communication Mechanisms Governing Ocular Lineage Specification from Human iPS Cells

The complexity of cell fate decisions that underpin early eye development can be effectively modelled by leveraging the unique properties of human induced pluripotent stem cells (hiPSCs). In this study, we have utilised transcriptomic data generated from hiPSCs as they begin to self-organise and differentiate into two-dimensional eye-like organoids in vitro, and employ advanced single-cell analytical tools to dissect the cellular communication networks that direct this dynamic process. We have identified key signalling mediators and transcriptional effectors that guide the transition from pluripotency through to ocular differentiation, and our analyses reveal the conservation of developmentally defined signalling pathways. Members of the Activin, FGF, BMP, WNT, and retinoic acid families of ligands and receptors displayed communication probabilities consistent with their ocular-specific developmental roles in vivo, and this was accompanied by conserved tissue-specific activity of transcriptional regulators. These findings not only highlight the utility of hiPSCs for studying the cellular interactions and molecular pathways that drive early developmental decisions, but also advance our understanding of eye development in an accessible stem cell-based system.