Programa de Recerca en Càncer, IMIM-Hospital del Mar, Barcelona, Spain.
Oncogene. 2013 Jul 11;32(28):3381-9. doi: 10.1038/onc.2012.342. Epub 2012 Aug 6.
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.
蜗牛 1 转录阻遏物在触发上皮-间充质转化中起着关键作用。虽然蜗牛 1 在早期发育中广泛表达，但在成年动物中，它仅限于一组间充质细胞，在这些细胞中，它具有一个很大程度上未知的功能。在这里，我们使用一种可诱导的蜗牛 1 耗竭的小鼠模型，证明了蜗牛 1对于维持间充质干细胞（MSCs）是必需的。这种作用与对转化生长因子（TGF）-β1 的反应性有关，TGF-β1 对其具有很强的依赖性。在条件敲除成年动物中耗竭蜗牛 1 会导致骨髓来源的 MSCs 数量显著减少。在培养中，缺乏蜗牛 1 的 MSC 过早地分化为成骨细胞或脂肪细胞，并且与对照相比，它们对 TGF-β1 诱导的分化阻断具有抗性。这些结果表明，蜗牛 1 在 TGF-β 反应和 MSC 维持中具有新的作用。
