RNA sequencing indicates age-dependent shifts in the cardiac fibroblast transcriptome between fetal, neonatal, and adult developmental ages

Cardiac fibroblasts are responsible for extracellular matrix turnover and repair in the cardiac environment and serve to help facilitate immune responses. However, it is well established that they have a significant phenotypic heterogeneity with respect to location, physiological conditions, and developmental age. The goal of this study was to provide an in-depth transcriptomic profile of cardiac fibroblasts derived from rat hearts at fetal, neonatal, and adult developmental ages to ascertain variations in gene expression that may drive functional differences in these cells at these specific stages of development. We performed RNA sequencing (RNA-seq) of cardiac fibroblasts isolated from fetal, neonatal, and adult rats and compared with the rat genome. Principal component analysis of RNA-seq data suggested that data variance was predominantly due to developmental age. Differential expression and gene set enrichment analysis against Gene Ontology and Kyoto Encyclopedia of Genes and Genomes datasets indicated an array of differences across developmental ages, including significant decreases in cardiac development and cardiac function-associated genes with age and a significant increase in immune- and inflammatory-associated functions, particularly immune cell signaling and cytokine and chemokine production, with respect to increasing developmental age. These results reinforce established evidence of diverse phenotypic heterogeneity of fibroblasts with respect to developmental age. Furthermore, based on our analysis of gene expression, age-specific alterations in cardiac fibroblasts may play a crucial role in observed differences in cardiac inflammation and immune response observed across developmental ages.