Mesenchymal cells emerge as primary contributors to fibrosis in multiple tissues

A longstanding controversy exists regarding the cellular origin of myofibroblasts in tissue fibrosis. A recent study by Hung and colleagues (Am J Respir Crit Care Med 188(7):820–830, 2013) used genetic fate mapping of FoxD1 embryonic progenitor cells to show a major and direct contribution of mesenchymal cells to fibrogenesis in the lung. Future studies using FoxD1‐specific inducible knockout models of pro‐fibrotic genes such as CCN2 will be valuable for determining anti‐fibrotic drug targets. The emergence of pericyte‐like myofibroblast precursors also raises the question of whether mesenchymal stem cells in various niches contribute to fibrotic responses throughout the body.