Cardiovascular disease remains the number one global cause of death and presents as multiple phenotypes in which the interplay between cardiomyocytes and cardiac fibroblasts (CFs) has become increasingly highlighted. Fetal and adult CFs influence neighboring cardiomyocytes in different ways. Thus far, a detailed comparison between the two is lacking. Using a genome-wide approach, we identified and validated 2 crucial players for maintaining the adult primary human CF phenotype. Knockdown of these factors induced significant phenotypical changes, including senescence and reduced collagen gene expression. These may now represent novel therapeutic targets against deleterious functions of CFs in adult cardiovascular disease.
Keywords: ATAC, assay for transposase accessible chromatin; ATAC-seq, assay for transposase accessible chromatin–sequencing; CF, cardiac fibroblast; CM, cardiomyocyte; ChIP-seq, chromatin immunoprecipitation–sequencing; ECM, extracellular matrix; EMT, epithelial-to-mesenchymal transformation; FGF, fibroblast growth factor; HCF, human cardiac fibroblast; IL, interleukin; IPA, Ingenuity Pathway Analysis; RNA-seq, ribonucleic acid–sequencing; RT-qPCR, reverse transcription–quantitative polymerase chain reaction; TF, transcription factor; aHCF, adult human cardiac fibroblast; cardiac fibroblasts; collagen; fHCF, fetal human cardiac fibroblast; histone methylation; transcriptome.