MYC is an early response regulator of human adipogenesis in adipose stem cells.

MYC is an early response regulator of human adipogenesis in adipose stem cells.
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DOI:
10.1371/journal.pone.0114133
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Thomas RS
Thomas RS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Deisenroth C;Black MB;Pendse S;Pluta L;Witherspoon SM;McMullen PD;Thomas RS

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脂肪干细胞(ASC)的分化对于脂肪组织的正常维持和功能是必要的。多能ASCs的获得和鉴定使研究驱动人类脂肪形成的分子决定因素成为可能。在这里,转录因子MYC被认为是ASC分化的重要调节因子。在分化初期,MYC转录本和蛋白的表达逐渐积累。使用siRNA介导的MYC基因敲除的功能丧失分析表明,激素刺激的脂肪生成受到抑制。MYC表现出一种早期和持续的表达模式,这种模式先于关键抑制基因的下调,以及转录和功能效应的诱导。糖皮质激素刺激被认为是MYC诱导的必要成分,并被发现以浓度依赖的方式影响脂肪形成。ASC中MYC基因敲除的全球基因表达分析丰富了与细胞黏附、细胞骨架重塑和脂肪形成的转录成分相关的功能通路。这些结果确定了MYC在促进多潜能ASC向成脂血统转化中的功能作用。
Adipose stem cell (ASC) differentiation is necessary for the proper maintenance and function of adipose tissue. The procurement and characterization of multipotent ASCs has enabled investigation into the molecular determinants driving human adipogenesis. Here, the transcription factor MYC was identified as a significant regulator of ASC differentiation. Expression of MYC transcript and protein was found to accumulate during the initial course of differentiation. Loss-of-function analysis using siRNA mediated knockdown of MYC demonstrated inhibition of hormonally stimulated adipogenesis. MYC exhibited an early and sustained expression pattern that preceded down regulation of key suppressor genes, as well as induction of transcriptional and functional effectors. Glucocorticoid stimulation was identified as a necessary component for MYC induction and was found to impact adipogenesis in a concentration-dependent manner. Global gene expression analysis of MYC knockdown in ASC enriched for functional pathways related to cell adhesion, cytoskeletal remodeling, and transcriptional components of adipogenesis. These results identify a functional role for MYC in promotion of multipotent ASC to the adipogenic lineage.
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发表时间: 1988-04-01
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