After injury, mesenchymal stromal cells (MSCs) contribute to tissue repair, but their differentiation capabilities need to be tightly regulated to avoid an excess of fibrotic scar tissue. Although the Wnt/β-catenin signalling pathway can affect fibrogenesis, the underlying mechanism is still poorly understood. In this study, Osvaldo Contreras, Enrique Brandan and colleagues (Contreras et al., 2020) demonstrate that transforming growth factor beta (TGF-β) regulates the expression of the T-cell factor or lymphoid enhancer factor (TCF/LEF) transcription factor TCF7L2 (also known as TCF4) in MSCs and fibroblasts. TCF7L2 interacts with β-catenin and is an effector of the Wnt pathway that regulates cell differentiation; it is highly expressed in MSCs and tissue-resident fibroblasts. Using glycerol-induced acute muscle damage as an injury model, the authors observe an initial upregulation of TCF7L2, before its levels are downregulated during recovery and MSC differentiation. Moreover, treatment of MSCs and fibroblasts with TGF-β decreases both the mRNA and protein levels of TCF7L2; this requires the transcriptional regulation activity of histone deacetylases and the participation of the ubiquitin–proteasome system. Finally, the authors show that TGF-β-mediated downregulation of TCF7L2 is specific to MSCs and fibroblasts and does not occur in myoblasts. This study thus uncovers a novel interplay between the Wnt and TGF-β pathways that regulates MSC fate and fibrosis.

• © 2020. Published by The Company of Biologists Ltd