• The interplay between cardiomyocytes and cardiac fibroblasts is increasingly being recognized as important in cardiac disease.
• Fetal and adult cardiac fibroblasts influence their neighboring cardiomyocytes in different ways. A genome-wide comparison of the 2 reveals that they share >80% of gene transcripts.
• Motif analysis of empirical regulatory elements located next to differentially expressed genes led to identification of key differential regulators of fibroblast identity.
• STAT1 and PLAGL1 were identified and validated as key transcription factors to maintain the adult cardiac fibroblast phenotype. Loss of either factor led to a significant change in phenotype, including smaller cell size, apoptosis, reduced turnover, and down-regulated collagen gene expression.
• Fetal and adult cardiac fibroblasts influence their neighboring cardiomyocytes in different ways. A genome-wide comparison of the 2 reveals that they share >80% of gene transcripts.
• Motif analysis of empirical regulatory elements located next to differentially expressed genes led to identification of key differential regulators of fibroblast identity.
• STAT1 and PLAGL1 were identified and validated as key transcription factors to maintain the adult cardiac fibroblast phenotype. Loss of either factor led to a significant change in phenotype, including smaller cell size, apoptosis, reduced turnover, and down-regulated collagen gene expression.