通过细胞循环调节,p65信号动态驱动了造血干细胞和祖细胞的发育进展
Clyde A Campbell1, Rodolfo Calderon2, Giulia Pavani3
1Department of Genetics, Development and Cell Biology; Iowa State University, Ames, IA, 50011, USA. clyde@iastate.edu.
Nature communications
|September 6, 2024
概括
核因子-kappa B (NF-kB) 信号传递就像一个时钟一样,控制着造血干细胞和原生细胞 (HSPC) 的发育. 暂时破坏NF-kB活动波导致斑马鱼和人类细胞的明显发育缺陷.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 血液形成 血液形成 血液形成
背景情况:
- 基因功能发现往往缺乏时间控制,忽视动态细胞信号传递.
- 细胞信号通路至关重要,但难以动态评估.
- 转录效应器的时间和空间再利用使信号通路分析复杂化.
研究的目的:
- 调查NF-kB信号传导在造血干细胞和原生细胞 (HSPC) 发育中的动态作用.
- 通过NF-kB在发育过程中发出信号来揭示细胞周期的时间调节.
- 评估NF-kB信号在人类造血发育中的功能性保存.
主要方法:
- 利用斑马鱼胚胎进行同步的发育过渡.
- 开发了定制的NF-kB记者斑马鱼胚胎与不稳定的光体实时信号动态.
- 在人类造血细胞发育研究中使用诱导多能干细胞 (iPSC) 模型.
主要成果:
- NF-kB信号功能作为HSPC进展的发育时钟,由两个p65活动波驱动.
- 这些p65活动波在特定的发育窗口中抑制细胞循环.
- NF-kB波的时间干扰导致HSPC损失 (受损规范) 或扩张和分层失败.
结论:
- 在HSPC发育过程中,NF-kB信号传递,特别是p65活性,是细胞周期的关键,以前未被识别的调节器.
- 促炎信号的时间对于正确的HSPC发育至关重要.
- 细胞信号应被视为一个动态的时间实体,以全面了解生物过程.
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