TAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation

TLDR

Mesenchymal stem cells can differentiate into multiple lineages, with Runx2 promoting osteogenesis and PPARγ driving adipogenesis. The study seeks to determine how Runx2 and PPARγ are regulated to specify these alternate cell fates. By altering TAZ expression in cell lines, mouse embryonic fibroblasts, primary MSCs, and zebrafish, the authors observed shifts in osteogenic versus adipogenic potential. TAZ coactivates Runx2-dependent transcription while repressing PPARγ-dependent transcription, acting as a molecular rheostat that modulates MSC differentiation.

Abstract

Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator–activated receptor γ (PPARγ), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3–binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while repressing PPARγ-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.