Snail1 controls TGF-β responsiveness and differentiation of mesenchymal stem cells

被引：53

作者：

Batlle, R. ^{[1
]}

Alba-Castellon, L. ^{[1
]}

Loubat-Casanovas, J. ^{[1
]}

Armenteros, E. ^{[1
]}

Franci, C. ^{[1
]}

Stanisavljevic, J. ^{[1
]}

Barderas, R. ^{[2
]}

Martin-Caballero, J. ^{[3
]}

Bonilla, F. ^{[4
]}

Baulida, J. ^{[1
]}

Casal, J. I. ^{[2
]}

Gridley, T. ^{[5
]}

Garcia de Herreros, A. ^{[1
,6
]}

机构：

[1] IMIM, Programa Recerca Cancer, Hosp Mar, Barcelona 08003, Spain

[2] CSIC, Dept Med Mol, Ctr Invest Biol, Madrid, Spain

[3] Parc Recerca Biomed Barcelona, Anim Facil, Barcelona, Spain

[4] Hosp Puerta Hierro, Serv Oncol Med, Majadahonda, Spain

[5] Maine Med Ctr Res Inst, Ctr Mol Med, Scarborough, ME USA

[6] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Barcelona, Spain

来源：

ONCOGENE | 2013年 / 32卷 / 28期

关键词：

Snail1; mesenchymal stem cells; TGF-beta; Akt; TRANSCRIPTION FACTOR SNAIL; NF-KAPPA-B; EXPRESSION; REPRESSOR; TRANSITIONS; PROTEIN; STROMA; BINDS; PTEN; AKT1;

D O I：

10.1038/onc.2012.342

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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)-beta 1 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-beta 1-induced differentiation block. These results demonstrate a new role for Snail1 in TGF-beta response and MSC maintenance.

引用

页码：3381 / 3389

页数：9

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