Integrating single‐cell and spatial transcriptomics delineates spatial gene expression patterns and molecular signatures of various tissues in mouse eyes

Aims/Purpose: The eye is a highly organized structure composed of well‐defined anatomical area with coordinated but distinct‐functional roles. This study aimed to elucidate spatial gene expression patterns and molecular signatures in different ocular tissues.

Methods: We performed spatial transcriptomics sequencing on normal mouse eye samples and integrated single‐cell transcriptomics and spatial transcriptomics for comprehensive bioinformatics analysis of eye. Findings regarding the discovery of several ligand‐receptor pairs and gene expression patterns were validated by in situ sequencing and immunofluorescence experiments.

Results: Firstly, we revealed the spatial gene expression patterns of ocular tissues and identified core spatial regulons of various tissues within the eye. Based on spatial transcriptomics analysis, we uncovered that the central retina prominently mediates synaptic signaling and ion channel transmission functions while the peripheral retina has significant visual reception and oxidative phosphorylation functions. In addition, this undertaking characterized critical neurotransmitters and spatial ligand‐receptor pairs action modes of distinct cell types within the retina, which might contribute to the maintenance of retinal electrical signal transmission. Furthermore, we simulated the spatial differentiation trajectories of lens and corneal cells, and delineated the spatial location dependent changes in gene expression profiles. Subsequently, we identified several novel spatial region‐specific regulators in lens and cell type‐specific regulators in cornea. Finally, we unveiled an ocular spatial organizational communication signaling system that dependent on candidate long‐distance inter‐tissue signaling molecule communication.

Conclusions: This undertaking is likely to aid forthcoming studies on the mechanisms of eye development, differentiation, regeneration and disease occurrence. Our dataset also serves as a scientific resource for atlas, but will also be useful in screening for molecular targets of eye lesions occurring in specific spatial locations, which will greatly improve our understanding of the mechanisms underlying the maintenance of ocular homeostasis in health and disease.