• Cardiac fibroblasts are a developmentally heterogeneous population, reported to have embryonic origins from the hematopoietic system, endothelium, epicardium, and neural crest.
• Cardiac fibroblasts play a key role in regulating normal myocardial integrity, as well as reverse remodeling that occurs after injury.
• Reactivation of certain developmental gene programs might prime a subset of fibroblast to be preferentially activated after myocardial injury.
• We characterize a combination of surface markers that can be used to prospectively identify and isolate the majority of cardiac fibroblasts using FACS (fluorescence-activated cell sorting).
• The cardiac fibroblast pool is primarily derived from the epicardial and endothelial lineages, with no ostensible contribution from hematopoietic or circulating cells.
• On injury, cardiac fibroblasts from different lineages exhibit similar proliferation rates and gene expression patterns, suggesting that cardiac fibroblasts are