Control of the Mesenchymal-Derived Cell Phenotype by Ski and Meox2: A Putative Mechanism for Postdevelopmental Phenoconversion

Abstract

The developing mesenchyme gives rise to a diverse host of important cell types, including fibroblasts, endothelial and smooth muscle cells. In postnatal tissues, stromal cells continue to differentiate into subtypes with specific functions, e.g., fibroblasts to myofibroblasts, but the molecular signals that govern their phenoconversion are incompletely understood. Herein, we provide a review of the function of c-Ski (Ski) and Meox2 transcription factors and provide a rationale to support our suggestion that these factors trigger the phenoconversion of "undifferentiated" parenchymal and stromal cells to variants with novel function. As phenoconversion events underlie both normal organ function and the pathogenesis of disease including cardiac fibrosis, we have developed a novel hypothesis to facilitate a clearer understanding of their underlying mechanisms.