刺激-反应信号的动态表征巨细胞的两极化状态
Apeksha Singh1, Supriya Sen1, Michael Iter1
1Signaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell systems
|June 6, 2024
概括
细胞微环境决定了细胞的功能. 研究巨细胞中核因子kB (NF-kB) 动态表明,细胞两极分化导致特殊功能,可以通过信号模式识别.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 免疫学 免疫学 免疫学
- 系统生物学 系统生物学
背景情况:
- 细胞功能是由它们的微环境塑造的.
- 极化细胞因子显著改变巨细胞的转录和表观基因组.
- 了解巨细胞对刺激的功能反应至关重要.
研究的目的:
- 描述分极分化的巨细胞群的功能反应.
- 测量转录因子核因子 κB (NF-κB) 对各种刺激的反应的动态.
- 开发基于动态信号模式区分细胞状态的方法.
主要方法:
- 测量单细胞NF-κB轨迹对6个极化巨细胞群的8个刺激的反应.
- 将机器学习应用于时间序列数据,以分析刺激区分能力.
- 识别信息轨迹特征 ("信号编码子") 用于细胞状态映射.
- 使用机械的NF-κB网络模型推断运动参数.
主要成果:
- 大细胞两极分化导致NF-κB动态中的刺激区分能力丧失,表明道化效应器功能.
- 确定了"信号编码子",使细胞状态景观的映射和条件化巨细胞的定位成为可能.
- 来自网络模型的动态参数提供了一个替代的细胞状态映射,并预测了生化发现.
结论:
- 单个分析物的动态轨迹,如NF-κB,可以区分功能细胞状态.
- 这种方法揭示了控制细胞行为的潜在分子网络状态.
- 这些发现为表征细胞状态及其功能专业化提供了一种新的方法.
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