转录因子CUX1在人类和小鼠脂肪细胞分化中发挥了相反的作用
Yang Chen1, Lin Liu1, Ryan P Calhoun1
1Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, United States; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, United States.
Molecular metabolism
|November 29, 2025
概括
转录因子CUX1在人类和小鼠之间的脂肪细胞分化中起着相反的作用. 了解这些物种特异性差异对于代谢性疾病研究至关重要.
科学领域:
- 代谢疾病和脂肪组织生物学.
- 脂肪生成的分子机制.
- 比较基因组学和转录基因组学.
背景情况:
- 脂肪细胞的分化对于健康的脂肪组织扩张和代谢平衡至关重要.
- 脂肪生成障碍有助于脂质缩,组织重塑和心脏代谢疾病.
- 像C/EBPβ这样的主转录因子启动脂肪生成程序.
研究的目的:
- 确定新型的C/EBPβ相关因素,调节人类脂肪细胞分化.
- 研究转录因子CUX1在脂肪生成中的作用.
- 为了比较CUX1在人类与小鼠脂肪细胞分化中的功能.
主要方法:
- 染色质免疫沉,然后选择性分离染色质相关蛋白 (ChIP-SICAP) 确定了CUX1作为C/EBPβ交互体.
- 在CRISPR/Cas9查和功能增加/丧失研究中,评估了CUX1对脂肪细胞前体细胞 (hAPC) 的影响.
- 通过RNA测序和ChIP测序阐明了CUX1-调节的基因和途径;在体内研究中使用了Cux1淘汰赛小鼠.
主要成果:
- CUX1的丧失损害了人类脂肪细胞的分化,而过度表达则增强了它.
- 在人体细胞中,CUX1促进了像PPARG这样的关键脂肪基因.
- 相反,CUX1抑制了人类脂肪细胞的分化,但在小鼠细胞中增强了分化,观察到明显的染色质结合模式.
- 在体内,Cux1在小鼠中的删除在肥胖发展过程中增加了de novo脂肪细胞的形成.
结论:
- 转录因子CUX1对人类和小鼠的脂肪细胞分化表现出相反的调节作用.
- 这些物种特异性功能强调了使用适当模型用于代谢疾病研究的重要性.
- 需要进一步研究CUX1在物种之间独特的调节机制.
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