在单个巨细胞中量化动态的促炎基因表达和异质性
Beverly Naigles1, Avaneesh V Narla2, Jan Soroczynski3
1Department of Molecular Biology, University of California San Diego, La Jolla, California, USA.
The Journal of biological chemistry
|September 9, 2023
概括
巨细胞中的亲炎性基因表达因干扰素- (IFNγ) 刺激动态而变化. IRF1对较低的IFNγ反应,而CXCL10/CXCL9需要更高的剂量,显示出显著的细胞对细胞的变异性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 系统生物学 系统生物学
背景情况:
- 巨细胞对于对病原体的免疫反应至关重要.
- 支持炎症的基因表达对于对抗感染至关重要.
- 炎症刺激的动态 (幅度和持续时间) 影响细胞反应.
研究的目的:
- 为了研究促炎基因 (IRF1,CXCL10,CXCL9) 如何响应巨细胞中的动态干扰素- (IFNγ) 刺激.
- 分析基因表达中的异质性.
- 模拟基因表达和异质性的潜在机制.
主要方法:
- 使用微流体装置进行长期活细胞成像.
- 对基因表达动态的定量分析.
- 确定性和随机计算模型的开发和应用.
主要成果:
- 通过低度或短时间的IFNγ诱导IRF1表达.
- CXCL10和CXCL9需要更高度或更长时间的IFNγ刺激.
- CXCL10和CXCL9表现出显著的细胞间变异性,CXCL10表现出很大程度上是随机的表达.
- 建模确定了一个缓慢的染色体开放步骤,有助于CXCL10异质性.
结论:
- 同一个通路内的促炎基因对动态IFNγ刺激表现出明显的响应特征.
- 上游信号适应和慢慢的染色体动力学有助于巨细胞中异质基因表达.
- 了解动态信号是解读免疫细胞反应的关键.
相关概念视频
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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