The Snail1 transcriptional repressor plays a key role in triggering epithelial-to-mesenchymal transition. Although Snail1 is widely expressed in early development, in adult animals it is limited to a subset of mesenchymal cells where it has a largely unknown function. Using a mouse model with inducible depletion of Snail1, here we demonstrate that Snail1 is required to maintain mesenchymal stem cells (MSCs). This effect is associated to the responsiveness to transforming growth factor (TGF)-β1 that shows a strong Snail1 dependence. Snail1 depletion in conditional knockout adult animals causes a significant decrease in the number of bone marrow-derived MSCs. In culture, Snail1-deficient MSCs prematurely differentiate to osteoblasts or adipocytes and, in contrast to controls, are resistant to the TGF-β1-induced differentiation block. These results demonstrate a new role for Snail1 in TGF-β response and MSC maintenance ; PMC3494751.-- et al. ; This study was funded by a grant awarded by la Fundación Científica de la Asociación Española contra el Cáncer to AGH, JIC and FB. Support from the Ministerio de Ciencia y Tecnología (SAF2006-00339 and SAF2010-16089) and Fundació La Marató de TV3 to AGH, and NIH R01HD034883 to TG is also appreciated. We also acknowledge support from ISCIII/FEDER (RD06/0020/0109, RD06/0020/0040, RD06/0020/0020), Generalitat de Catalunya (2009SGR867). RB and LA-C were recipients from FPI predoctoral fellowships