Comment: The heterogeneity of cardiac fibroblasts (CFs), the key cell types involved in maladaptive myocardial remodelling is not a novelty. On the other hand, there is still no evidence of specific CFs populations that participate in distinct phases of myocardial healing process following ischemic injury.
By characterising the cellular populations genetically tagged by Collagen1α1 expression with single cell RNA sequencing, Ruiz-Villalba and Colleagues identified a subset of cardiac fibroblasts (named reparative cardiac fibroblasts, RCF) expressing the Collagen Triple Helix Repeat Containing 1 (CTHRC1) gene, specifically involved in early cardiac healing after induction of myocardial ischemia. Interestingly, if these cells were genetically ablated by CTHRC1 knock-out, MI consequences were more severe with increase in ventricular rupture. Using RNA velocity, the authors define the dynamic evolution of RCF inside the infarcted myocardium and define a transcriptional signature putatively involved in control of their phenotype, dependent on SOX-9 and canonical/non-canonical TGF-β signalling. Finally, they validate their findings in a swine model of MI and in myocardial samples of patients with infarct.
The finding of a CF subset with peculiar myocardial reparative functions gives new hopes for time-specific modulation of cardiac repair process at defined stages after infarction with hopes of reducing the burden of maladaptive myocardial remodelling.
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