TY - JOUR TI - TGF-β-driven downregulation of the transcription factor TCF7L2 affects Wnt/β-catenin signaling in PDGFRα+ fibroblasts AU - Contreras, Osvaldo AU - Soliman, Hesham AU - Theret, Marine AU - Rossi, Fabio M. V. AU - Brandan, Enrique T2 - Journal of Cell Science AB - Skip to Next Section Mesenchymal stromal cells (MSCs) are multipotent progenitors essential for organogenesis, tissue homeostasis, regeneration and scar formation. Tissue injury upregulates transforming growth factor β (TGF-β) signaling, which modulates myofibroblast fate, extracellular matrix remodeling and fibrosis. However, the molecular determinants of MSC differentiation and survival remain poorly understood. During canonical Wnt signaling, T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors regulate development and stemness, but the mechanisms by which injury-induced cues modulate their expression remain underexplored. Here, we studied the cell type-specific gene expression of TCF/LEF transcription factors and, more specifically, we investigated whether damage-induced TGF-β signaling impairs the expression and function of TCF7L2 (also known as TCF4), using several models of MSCs, including skeletal muscle fibro-adipogenic progenitors. We show that TCF/LEFs are differentially expressed and that TGF-β reduces the expression of TCF7L2 in MSCs but not in myoblasts. We also found that the ubiquitin–proteasome system regulates TCF7L2 proteostasis and participates in TGF-β-mediated TCF7L2 protein downregulation. Finally, we show that TGF-β requires histone deacetylase activity to repress the expression of TCF7L2. Thus, our work reports a novel interplay between TGF-β and canonical Wnt signaling cascades in PDGFRα+ fibroblasts and suggests that this mechanism could be targeted in tissue repair and regeneration. DA - 2020/06/15/ PY - 2020 DO - 10.1242/jcs.242297 DP - jcs.biologists.org VL - 133 IS - 12 J2 - J Cell Sci LA - en SN - 0021-9533, 1477-9137 UR - https://jcs.biologists.org/content/133/12/jcs242297 Y2 - 2020/06/19/22:06:27 ER -