SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage

被引：188

作者：

Seo, Eunjeong ^{[2
]}

Basu-Roy, Upal ^{[1
]}

Gunaratne, Preethi H. ^{[3
]}

Coarfa, Cristian ^{[4
]}

Lim, Dae-Sik ^{[2
]}

Basilico, Claudio ^{[1
]}

Mansukhani, Alka ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

[2] Korea Adv Inst Sci & Technol, Natl Creat Initiat Ctr Cell Div & Differentiat, Dept Biol Sci, Taejon 305701, South Korea

[3] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA

[4] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

CELL REPORTS | 2013年 / 3卷 / 06期

关键词：

ORGAN SIZE CONTROL; HIPPO PATHWAY; CONTACT INHIBITION; TISSUE REGENERATION; SELF-RENEWAL; BONE-MARROW; WNT; TRANSCRIPTION; GROWTH; TAZ;

D O I：

10.1016/j.celrep.2013.05.029

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The osteoblastic and adipocytic lineages arise from mesenchymal stem cells (MSCs), but few regulators of self-renewal and early cell-fate decisions are known. Here, we show that the Hippo pathway effector YAP1 is a direct target of SOX2 and can compensate for the self-renewal defect caused by SOX2 inactivation in osteoprogenitors and MSCs. Osteogenesis is blocked by high SOX2 or YAP1, accelerated by depletion of either one, and the inhibition of osteogenesis by SOX2 requires YAP1. SOX2 favors adipogenesis and induces PPAR gamma, but adipogenesis can only occur with moderate levels of YAP1. YAP1 induction by SOX2 is restrained in adipogenesis, and both YAP1 overexpression and depletion inhibit the process. YAP1 binds beta-catenin and directly induces the Wnt antagonist Dkk1 to dampen pro-osteogenic Wnt signals. We demonstrate a Hippo-independent regulation of YAP1 by SOX2 that cooperatively antagonizes Wnt/beta-catenin signals and regulates PPAR gamma to determine osteogenic or adipocytic fates.

引用

页码：2075 / 2087

页数：13

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