TAZ, a transcriptional modulator of mesenchymal stem cell differentiation
TAZ, a transcriptional modulator of mesenchymal stem cell differentiation
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DOI：
10.1126/science.1110955
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发表时间：
2005-08-12
期刊：
影响因子：
56.9
通讯作者：
Yaffe, MB
中科院分区：
文献类型：
--
作者：
Hong, JH;Hwang, ES;Yaffe, MB
间充质干细胞（MSC）是一种多能细胞类型，可以分化成几个不同的谱系。两个关键的转录因子Runx 2和过氧化物酶体增殖物激活受体γ（PPAR γ）分别驱动MSC分化为成骨细胞或脂肪细胞。这两个转录因子如何被调节以指定这些交替的细胞命运仍然是一个关键问题。在这里，我们报告，14-3-3结合蛋白，TAZ（转录辅激活因子与PDZ结合基序），共激活Runx 2依赖的基因转录白色抑制PPAR γ依赖的基因转录。通过调节TAZ在模型细胞系、小鼠胚胎成纤维细胞和培养中的原代间充质干细胞以及体内斑马鱼中的表达，我们观察到成骨与成脂潜能的改变。这些结果表明，TAZ的功能作为一个分子变阻器，调节MSC分化。
Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator-activated receptor gamma (PPAR gamma), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3-binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription white repressing PPAR gamma-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.