Key result
The inducible NG2 CreER driver optimally targets cardiac pericytes in mice without significant labeling of fibroblasts, whereas the PDGFRβ CreER line lacks specificity.
Why the study?
Studies on the role of myocardial pericytes in heart disease have been hampered by confusion with other interstitial cell types and a lack of specific tools for their identification, lineage tracing, and conditional targeting.
The inducible NG2 CreER driver is a specific and reliable genetic tool for targeting cardiac pericytes in mice, overcoming the lack of specificity seen with other drivers like PDGFRβ CreER.
Validates NG2 CreER for precise cardiac pericyte studies in mice; leaves open broader model applicability and human translation.
Background In the myocardium, pericytes are often confused with other interstitial cell types, such as fibroblasts. The lack of well‐characterized and specific tools for identification, lineage tracing, and conditional targeting of myocardial pericytes has hampered studies on their role in heart disease. In the current study, we characterize and validate specific and reliable strategies for labeling and targeting of cardiac pericytes. Methods and Results Using the neuron‐glial antigen 2 (NG2) DsRed reporter line, we identified a large population of NG2+ periendothelial cells in mouse atria, ventricles, and valves. To examine possible overlap of NG2+ mural cells with fibroblasts, we generated NG2 DsRed ; platelet‐derived growth factor receptor (PDGFR) α EGFP pericyte/fibroblast dual reporter mice. Myocardial NG2+ pericytes and PDGFRα+ fibroblasts were identified as nonoverlapping cellular populations with distinct transcriptional signatures. PDGFRα+ fibroblasts expressed high levels of fibrillar collagens, matrix metalloproteinases, tissue inhibitor of metalloproteinases, and genes encoding matricellular proteins, whereas NG2+ pericytes expressed high levels of Pdgfrb , Adamts1 , and Vtn . To validate the specificity of pericyte Cre drivers, we crossed these lines with PDGFRα EGFP fibroblast reporter mice. The constitutive NG2 Cre driver did not specifically track mural cells, labeling many cardiomyocytes. However, the inducible NG2 CreER driver specifically traced vascular mural cells in the ventricle and in the aorta, without significant labeling of PDGFRα+ fibroblasts. In contrast, the inducible PDGFRβ CreER line labeled not only mural cells but also the majority of cardiac and aortic fibroblasts. Conclusions Fibroblasts and pericytes are topographically and transcriptomically distinct populations of cardiac interstitial cells. The inducible NG2 CreER driver optimally targets cardiac pericytes; in contrast, the inducible PDGFRβ CreER line lacks specificity.
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A 2021 study studied this question. Inducible NG2 CreER driver vs. Inducible PDGFRβ CreER line was evaluated on Specificity of pericyte Cre drivers. The inducible NG2 CreER driver optimally targets cardiac pericytes in mice without significant labeling of fibroblasts, whereas the PDGFRβ CreER line lacks specificity.
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