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单细胞转录学揭示了出生至5岁之间对脂多糖的发育调节反应的细胞类型特征

James F Read^1,2, Michael Serralha², Jesse D Armitage^2,3

¹Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, United States.

Frontiers in immunology

|November 3, 2023

概括

新生儿对脂聚糖 (LPS) 和Poly (I:C) 的免疫反应显著不同,LPS反应在5岁时成熟. 这项研究揭示了关键的基因调控网络,推动了早期免疫力中的这些变化.

科学领域:

免疫学免疫学免疫学
发展生物学发展生物学
基因组学就是基因组学.

背景情况:

新生儿免疫系统对环境刺激和病原体进行了显著的适应.
从出生到幼儿时代的免疫系统发展背后的分子机制仍然不太清楚.
单细胞基因组学为早期生命中的免疫基因表达变化提供了高分辨率的见解.

研究的目的:

在生命早期先天免疫激活后,研究基因表达程序的变化.
用单细胞RNA测序来比较出生时的免疫反应与5岁时的免疫反应.
在早期发育过程中确定控制免疫细胞功能的关键调节机制.

主要方法:

单细胞RNA测序 (scRNA-seq) 在带血中的单核细胞上进行,并与5年的外周血液相匹配.
细胞用脂多糖 (LPS) 和聚氨酸 (Poly) 刺激了18小时.
对基因调节网络和细胞间通信进行了分析.

主要成果:

脂聚糖 (LPS) 诱导了新生儿单细胞和淋巴细胞中干扰素 (IFN) 信号的受约束的炎症反应.
聚氨酸 (Poly(I:C)) 在两个时间点都引起了所有细胞类型的强大的IFN信号响应.
在出生和5岁之间,免疫反应中的细胞对细胞通信得到加强;在LPS刺激时观察到不同的单细胞激活轨迹.

结论:

免疫细胞对先天性刺激的反应在出生和5岁之间显著成熟.
像IRF1,STAT1和IRF7这样的关键监管机构参与LPS诱导的IFN信号传输,并可能发挥发展作用.
研究结果提供了对早期生命免疫力和感染易感性的基因调节格局的见解.

关键词:

这是带血,带血.干扰子干扰子干扰子脂多糖类糖化物 (Lipopolysaccharide) 是一种多脂多糖的化合物.聚I:C) 是一个多I:C) 是一个多I:C) 是一个多I:C) 是一个多I:C).这是一种亲炎症性炎症.这就是 scRNA-Seqq.单细胞基因组学单细胞基因组学类似于收费的受体.

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