Skip to main content
. Author manuscript; available in PMC: 2017 Feb 1.
Published in final edited form as: J Mol Cell Cardiol. 2015 Dec 22;91:52–60. doi: 10.1016/j.yjmcc.2015.12.016

Figure 1. Fibroblast and myofibroblast origins.

Figure 1

Multiple cell types have been hypothesized to differentiate or transdifferentiate into myofibroblasts including pericytes/vascular smooth muscle cells (VSMC), circulating monocytes and fibrocytes, endothelial cells, epicardial and mesenchymal cells, and quiescent fibroblasts. In development, quiescent fibroblasts primarily differentiate from epicardial and mesenchymal cells in a mechanism known as epithelial-to-mesenchymal transition (EMT). EMT is largely governed by TGFβ signaling through SMAD proteins and the MRTF and TCF21 transcription factors. Disease can cause fibroblasts to differentiate into myofibroblasts and cause tissue fibrosis. Resolution of fibrosis can occur through two mechanisms: apoptosis or dedifferentiation. Myofibroblasts that dedifferentiate into quiescent fibroblasts may also further transdifferentiate into endothelial cells in a p53-dependent manner. Chronic disease often results in cardiomyocyte death, and reprogramming fibroblasts into cardiomyocytes may offer potential therapies to reduce fibrosis.