Table 1. Cardiac fibroblast markers.
Fibroblast marker | Sensitivity (expressed in all CFs or only in subpopulations?) | Specificity (expressed only in CFs or also in other cells?) | Accessibility for antibody detection (cellular location) | Mouse models (Cre-mouse for lineage tracing/reporter mouse) | Notes |
---|---|---|---|---|---|
Ddr2 | Low (only small percentage of CFs) | Medium (also by lymphocytic lineages, SMCs, ECs) | Good (surface) | No/No | – |
CD90 | Medium (subset of fibroblasts: 65–85%) | Medium (also on immune cells and endothelial lineages) | Good (surface) | Yes (Thy1.2-Cre)/No | – |
Pdgfrα | High | High-Medium (disease setting: also in SMCs, CMs; development: also in cardiovascular progenitor cells) | Good (surface) (however, antibodies seem to work only for IHC not for FACS) | Yes (tamoxifen-inducible)/Yes | Emerging as a definitive marker of CFs in adult tissues |
Vimentin | High (in all CFs) | Low (also in the entire endothelial lineage, SMCs, pericytes) | Medium (intracellular) | No/No | – |
Fsp1 | Low (only small subset of CFs → perivascular, not interstitial); Fsp1+ CFs rare in the normal heart | Low (also in inflammatory leukocytes and vascular cells after MI and TAC; marks monocytes, SMCs, ECs, CMs) | Medium (intracellular) | Yes (Fsp1-Cre mouse)//Yes (Fsp1-GFP reporter mouse) | In resting and activated CFs |
Tcf21 | Medium (subset of fibroblasts) | High-medium (also in other proepicardial lineages) | Medium-low (nucleus → transcription factor) | Yes (Tcf21-iCre)/ Yes (Tcf21-LacZ) | Unknown how robust the expression of Tcf21 is in normal or injured adult hearts |
Postn | Low (only small percentage of CFs; ~10% in the homeostatic heart) | High (specifically by epicardial derived myofibroblasts) | Low (secreted → ECM protein) | Yes (Postn-Cre mouse)/Yes (Postn-LacZ) | Robustly up-regulated after injury → useful marker of myofibroblasts |
Col1a1 | High (Col1a1-CFs are positive for Vim and Pdgfrα) | Medium (also in osteoblasts, odontoblasts, SMCs, mesenchymal cells) | Low (secreted → ECM protein) | Yes/Yes | – |
MEFSK4 | Not analyzed | High-medium (also detects pericytes, granulocytes) | Good (surface) | No/No | ONLY in mouse! |
CF, cardiac fibroblasts; SMCs, smooth muscle cells; ECs, endothelial cells; CMs, cardiomyocytes; IHC, immunohistochemical staining; FACS, fluorescent activated cell sorting; MI, myocardial infarction; TAC, transverse aortic constriction; ECM, extracellular matrix; Cre, Cre-recombinase.