Snail1 controls TGF-β responsiveness and differentiation of mesenchymal stem cells.
Snail1 controls TGF-β responsiveness and differentiation of mesenchymal stem cells.
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DOI：
10.1038/onc.2012.342
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发表时间：
2013-07-11
期刊：
影响因子：
8
通讯作者：
Garcia de Herreros, A.
中科院分区：
文献类型：
--
作者：
Batlle, R.;Alba-Castellon, L.;Loubat-Casanovas, J.;Armenteros, E.;Franci, C.;Stanisavljevic, J.;Barderas, R.;Martin-Caballero, J.;Bonilla, F.;Baulida, J.;Casal, J. I.;Gridley, T.;Garcia de Herreros, A.
Snail1转录抑制因子在触发上皮细胞向间质细胞转化中起关键作用。尽管Snail1在早期发育中广泛表达，但在成年动物中，它仅限于间充质细胞的一个亚群，其功能在很大程度上是未知的。通过诱导Snail1缺失的小鼠模型，我们证明了Snail1是维持间充质干细胞（MSCs）所必需的。这种效应与对TGF-β1的响应性有关，表现出强烈的Snail1依赖性。在条件敲除的成年动物中，snail1缺失导致骨髓来源的间充质干细胞数量显著减少。在培养中，snail1缺失的MSCs过早地分化为成骨细胞或脂肪细胞，与对照组相比，它们对TGF-β1诱导的分化阻断具有抗性。这些结果表明Snail1在TGF-β反应和MSC维持中具有新的作用。
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 TGF-β1 which shows a strong Snail1 dependence. Snail1-depletion in conditional knock-out 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.
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