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.