Hippo信号通路转录效应因子TAZ/YAP对间充质干细胞分化的调控
收稿日期: 2013-05-06
修回日期: 2013-07-14
网络出版日期: 2013-10-25
基金资助
国家自然科学基金项目(编号：31272520)和黑龙江省自然科学基金项目(编号：C201215)资助
Regulation of differentiation of mesenchymal stem cells by the Hippo pathway effectors TAZ/YAP
Received date: 2013-05-06
Revised date: 2013-07-14
Online published: 2013-10-25
间充质干细胞(Mesenchymal stem cells, MSCs)是一种多能性细胞, 可分化为软骨细胞、脂肪细胞、肌细胞等不同世系细胞。一些世系特异性转录因子, 如Runt相关转录因子2 (Runt related transcription factor 2, RUNX2)、过氧化物增殖子激活型受体γ (Peroxisome proliferator-activator receptor gamma, PPARγ)、肌发生分化因子1(Myogenic differentiation 1, MyoD)等在MSCs分别向成骨、脂肪和生肌细胞分化过程中具有关键的调控作用。近几年研究发现, Hippo信号通路可通过其转录效应因子TAZ (Tafazzin)/YAP(Yes-associated protein)对上述世系特异性转录因子进行调控, 从而影响MSCs的分化方向。TAZ与RUNX2结合可增强骨发生程序的执行并促进MSCs向成骨分化, 而与PPAR-γ结合则会抑制MSCs向脂肪细胞方向分化。在MSC样细胞中, TAZ异位表达会以一种MyoD依赖方式增加生肌基因表达并加速肌纤维生成。此外, BMP-2、TNF-α、Eph-Ephrin等信号通路, 小分子药物(KR62980、TM-25659等)以及机械刺激都可通过调控Hippo信号通路转录效应因子TAZ/YAP活性影响MSCs的命运决定。文章综述了哺乳动物Hippo信号通路的转导途径, 转录效应因子TAZ/YAP与间充质世系特异性转录因子的作用机理, 及与其他信号通路相互作用对MSCs分化的影响。
门通 朴善花 滕春波 . Hippo信号通路转录效应因子TAZ/YAP对间充质干细胞分化的调控[J]. 遗传, 2013 , 35(11) : 1283 -1290 . DOI: 10.3724/SP.J.1005.2013.01283
Mesenchymal stem cells (MSCs) are pluripotent cells which can differentiate into several distinct lineages, such as chondrocytes, adipocytes and myofibers. It has been reported that the lineage-specific transcriptional factors including Runt related transcription factor 2 (RUNX2), Peroxisome proliferator-activator receptor gamma (PPARγ) and Myogenic differentiation 1 (MyoD) may play key regulatory roles among the differentiation of MSCs. Recently, researches have confirmed that the Hippo pathway impacts the differentiation fates of MSCs through regulating the activity of line-age-specific transcription factors by the Hippo pathway effectors Tafazzin (TAZ) and/or Yes-associated protein (YAP). The interaction between TAZ and RUNX2 boosts the osteogenic processes and promotes MSCs differentiating into osteoblast lineage. However, PPARγ binding to TAZ may inhibit the adipocytes differentiation, and thus overexpression of TAZ in mesenchymal stem cell-like cells increases the expression of myogenic genes and hastens myofiber formation through a MyoD-dependent manner. Moreover, other signaling pathways (such as BMP-2, TNF-α, Eph-Ephrin, etc.), small molecules (KR62980, TM-25659, etc.), and mechanistic stimuli can also affect the fate by regulating the activity of TAZ/YAP. In this review, we summarized the signaling pattern of Hippo pathway and the function mechanism of TAZ and/or YAP by enu-merating their interaction to several lineage-specific transcriptional factors and relationship with other signal pathways dur-ing MSCs differentiation.
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