通过调节H2B表达,ATF3诱导可以防止骨肌肉干细胞过早激活
Suyang Zhang1,2, Feng Yang3, Yile Huang3
1Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Nature communications
|August 17, 2023
概括
激活转录因子3 (ATF3) 阻止了骨肌肉干细胞过早激活. ATF3通过调节肌肉再生和预防衰老至关重要的基因组2B来维持干细胞池.
科学领域:
- 肌肉干细胞生物学 肌肉干细胞生物学
- 再生医学是一种再生医学.
- 细胞周期控制的分子机制
背景情况:
- 骨肌肉干细胞 (卫星细胞,SCs) 对于肌肉平衡和受伤后的修复至关重要.
- 控制SC激活和细胞循环进入损伤时的精确机制尚未完全理解.
- 维持SC池对于长期的肌肉再生能力至关重要.
研究的目的:
- 研究激活转录因子3 (ATF3) 在调节骨肌肉干细胞激活中的作用.
- 阐明ATF3影响SC行为和肌肉再生的分子机制.
- 为了确定ATF3对SC池维护和预防衰老的影响.
主要方法:
- 骨肌干细胞中Atf3的遗传删除 (短期和长期).
- 分析急性损伤后和运动期间的SC激活和肌肉再生.
- 分子测试用于评估基因转录 (基因组2B) 和细胞过程 (核细胞位移,基因组不稳定,衰老).
主要成果:
- 短期Atf3删除加速了急性受伤诱导的再生,而长期删除导致SC池耗尽和再生受损.
- 在自愿运动期间,ATF3损失诱导了SC激活,并在耐力运动期间放大了激活.
- ATF3直接上调Histone 2B基因表达,抑制核细胞位移和过早的基因转录,从而防止SC激活,基因组不稳定性和衰老.
结论:
- 激活转录因子3 (ATF3) 作为早期骨肌干细胞激活的关键抑制剂.
- 通过调节2B基因组的表达,ATF3保护了SC池,并确保了有效的肌肉再生.
- 这项研究揭示了一种新的机制,涉及ATF3介导的早期激活的抑制,以维持SC功能并防止衰老.
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