Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells
Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells
复制标题
DOI：
10.1073/pnas.1109409108
复制
发表时间：
2011-09-27
影响因子：
11.1
通讯作者：
Lazar, Mitchell A.
中科院分区：
文献类型：
--
作者：
Cristancho, Ana G.;Schupp, Michael;Lazar, Mitchell A.
确定脂肪细胞前体潜能的因素对肥胖有重要意义。前脂肪细胞是成纤维细胞样细胞，致力于成为圆形的载脂脂肪细胞。在体外，这种分化过程是由融合促进的，然后是脂肪形成刺激。在脂肪形成过程中，大量的细胞结构基因在脂肪细胞基因诱导之前被抑制。在这里，我们报告的转录抑制因子转录因子7样1（TCF7L1）结合，并直接调节细胞结构基因的表达。TCF7L1的消耗抑制分化，因为TCF7L1间接诱导脂肪形成转录因子过氧化物酶体增殖物激活受体。这种方式可以通过抑制肌球蛋白II活性来替代。TCF7L1在成脂细胞系中通过细胞接触诱导，并且TCF7L1的异位表达证实了前体细胞向脂肪细胞分化的融合要求。相比之下，TCF 7L1在非成脂成纤维细胞的融合期间不被诱导，并且值得注意的是，TCF 7L1的强制表达足以使非成脂成纤维细胞进入成脂命运。这些结果确立了TCF7L1作为一个转录枢纽，协调细胞与细胞之间的接触，并具有脂肪形成能力所需的转录抑制作用。
The identification of factors that define adipocyte precursor potential has important implications for obesity. Preadipocytes are fibroblastoid cells committed to becoming round lipid-laden adipocytes. In vitro, this differentiation process is facilitated by confluency, followed by adipogenic stimuli. During adipogenesis, a large number of cytostructural genes are repressed before adipocyte gene induction. Here we report that the transcriptional repressor transcription factor 7-like 1 (TCF7L1) binds and directly regulates the expression of cell structure genes. Depletion of TCF7L1 inhibits differentiation, because TCF7L1 indirectly induces the adipogenic transcription factor peroxisome proliferator-activated receptor. in a manner that can be replaced by inhibition of myosin II activity. TCF7L1 is induced by cell contact in adipogenic cell lines, and ectopic expression of TCF7L1 alleviates the confluency requirement for adipocytic differentiation of precursor cells. In contrast, TCF7L1 is not induced during confluency of non-adipogenic fibroblasts, and, remarkably, forced expression of TCF7L1 is sufficient to commit non-adipogenic fibroblasts to an adipogenic fate. These results establish TCF7L1 as a transcriptional hub coordinating cell-cell contact with the transcriptional repression required for adipogenic competency.