Wnt signaling and adipocyte lineage commitment
Wnt signaling and adipocyte lineage commitment
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DOI：
10.4161/cc.7.9.5815
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发表时间：
2008-05-01
期刊：
影响因子：
4.3
通讯作者：
Lane, M. Daniel
中科院分区：
文献类型：
--
作者：
Bowers, Robert R.;Lane, M. Daniel
肥胖的特征是成熟脂肪细胞数量增加。这些新生脂肪细胞来源于前脂肪细胞，而前脂肪细胞又来源于间充质干细胞（MSC）。由于对控制间充质干细胞向前脂肪细胞转化的机制知之甚少，因此对脂肪形成中的这一早期事件进行了进一步研究。使用C3 H10 T1/2细胞（10 T1/2细胞）作为MSC模型，并将来源于这些细胞的定向A33前脂肪细胞系用作前脂肪细胞的模型。微阵列技术被用来确定差异表达的基因在多能10 T1/2细胞相比，A33前脂肪细胞。芯片和实时荧光定量RT-PCR分析表明，Wnt信号通路的几个关键基因在10 T1/2和A33细胞中差异表达。特别令人感兴趣的是，R-spondins-2和-3，新描述的激活经典Wnt信号通路的分子，在增殖的A33细胞中与10 T1/2细胞相比显著上调。与这些发现相一致，β-连环蛋白在增殖的A33细胞的细胞核中积累，而不是在10 T1/2细胞的细胞核中。此外，参与Wnt信号传导的转录因子的Lef/Tcf家族的几个成员也在10 T1/2和A33细胞之间差异表达。这些和其他发现表明Wnt信号的激活是脂肪形成的早期事件。
Obesity is characterized by an increase in the number of mature fat cells. These nascent adipocytes are derived from preadipocytes, which in turn are derived from mesenchymal stem cells (MSCs). Since little is known about the mechanisms controlling the commitment of MSCs into preadipocytes, this early event in adipogenesis was further investigated. C3H10T1/2 cells (10T1/2 cells) were employed as a MSC model and a committed A33 preadipocyte cell line derived from these cells served as a model of preadipocytes. Microarray technology was used to identify genes that are differentially expressed in pluripotent 10T1/2 cells when compared with A33 preadipocytes. Several key genes of the Wnt signaling pathway were differentially expressed between 10T1/2 and A33 cells as demonstrated by microarray and quantitative real-time RT-PCR analyses. Of particular interest, R-spondins-2 and -3, newly described molecules that activate the canonical Wnt signaling pathway, are markedly upregulated in proliferating A33 cells compared to 10T1/2 cells. Consistent with these findings beta-catenin accumulates in the nuclei of proliferating A33 cells, but not 10T1/2 cells. In addition, several members of the Lef/Tcf family of transcription factors involved in Wnt signaling are also differentially expressed between 10T1/2 and A33 cells. These and other findings indicate that activation of Wnt signaling is an early event in adipogenesis.