Multi-species single-cell transcriptomic analysis of ocular compartment regulons

Area of Science:

• Ophthalmology
• Genomics
• Cell Biology

Background:

• Single-cell RNA sequencing (scRNA-seq) has profiled various species' retinas.
• A lack of integrative, cross-species retinal research exists.
• Understanding ocular cell types and gene regulation is vital for eye health.

Purpose of the Study:

• To create the first single-cell atlas of human and porcine ocular compartments.
• To investigate inter-species retinal differences and identify ocular stem cells.
• To map eye disease genes, analyze cell regulons, and explore conserved factors.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of human and porcine ocular tissues.
• Construction of a cross-species single-cell atlas.
• Analysis of gene expression, transcription factors, and receptor-ligand interactions.
• Investigation of gene conservation across vertebrates.

Main Results:

• The first integrated single-cell atlas of human and porcine ocular compartments was generated.
• Putative adult stem cells in iris tissue were identified.
• A disease map of eye disorder genes was created.
• Unique directional signaling pathways between ocular cell types were revealed.
• Conservation of gene regulatory networks (regulons) across vertebrates was studied.
• KLF7 was identified as critical for retinal ganglion cell differentiation and maturation.

Conclusions:

• This study establishes a foundational cross-species ocular cell atlas.
• KLF7 plays a significant role in retinal ganglion cell maturation.
• The findings provide insights into eye development, disease, and conserved regulatory mechanisms.