Abstract 19111: Multipotent Mesp1 Progenitors Contribute to a Population of Cardiac Fibroblasts During Development and After Injury
Mesp1 is considered as a master regulator for cardiovascular development. It has previously been shown that progenitor cells expressing Mesp1 contribute to the cardiovascular lineage, including cardiomyocytes, endothelial and vascular smooth muscle cells. To date, no direct link between progenitor cells expressing Mesp1 and cardiac fibroblasts has been reported. We hypothesized that cardiovascular progenitors expressing Mesp1 during early development also give rise to the cardiac mesenchyme. We performed lineage tracing experiments to identify the precursors of cardiac fibroblasts. We generated Mesp1Cre mT/mG mice, in which Mesp1-derived progenies are indelibly labeled GFP. We used fluorescent activated cell sorting (FACS) to isolate fibroblasts using Thy1 as an inclusive surface marker for fibroblasts and excluding hematopoietic markers (CD45, Ter119), macrophages (Cd11b) and endothelial cells (CD31). Our results showed that the majority of cardiac fibroblasts (> 75%) are derived from Mesp1-expressing cells. Cardiac fibroblasts (derived from Mesp1-expressing and Mesp1-nonexpressing cells) were cultured in vitro and positive for fibroblast markers after 3 passages with a dose dependent response to TGFβ treatment. Immunostaining of the adult heart tissue sections also showed presence of fibroblasts derived from both Mesp1 and non-Mesp1 progenitors. In order to determine whether these cells respond differentially to cardiac fibrosis, we performed transaortic constriction and sham surgery on the transgenic mice. Our data shows that the relative proportion of Mesp1-derived fibroblasts remains the same despite proliferation after pressure overload, suggesting that fibroblast division upon injury is not restricted to certain developmentally restricted fibroblast populations. In summary, we provide evidence that cardiac fibroblasts may share a common embryonic origin with the cardiovascular lineages.
- © 2013 by American Heart Association, Inc.