Keratocyte gene expression shaped by ECM dimensionality: Evidence for enhanced quiescence in 3D culture

Previous work has demonstrated that varying ECM dimensionality (3D vs. 2D) and structure (fibrillar vs. non-fibrillar) can produce distinct cell phenotypes; however, the transcriptional changes underlying how cells sense and respond to these different environments are not well understood.

Here, we used bulk RNA sequencing to compare the gene expression profiles of primary rabbit corneal keratocytes cultured on collagen-coated substrates and on top of or embedded within fibrillar collagen matrices under serum-free conditions. Differential expression and functional analyses revealed distinct transcriptional profiles across the culture conditions and identified differentially expressed genes and enriched signaling pathways primarily related to the ECM, cell-matrix interactions, cell mechanics, and proliferation.