Biozentrum, University of Basel, Switzerland.
Swiss Institute of Bioinformatics, Basel, Switzerland.
FEBS Lett. 2022 Oct;596(20):2630-2643. doi: 10.1002/1873-3468.14478. Epub 2022 Sep 2.
The origin of functional heterogeneity among macrophages, key innate immune system components, is still debated. While mouse strains differ in their immune responses, the range of gene expression variation among their pre-stimulation macrophages is unknown. With a novel approach to scRNA-seq analysis, we reveal the gene expression variation in unstimulated macrophage populations from BALB/c and C57BL/6 mice. We show that intrinsic strain-to-strain differences are detectable before stimulation and we place the unstimulated single cells within the gene expression landscape of stimulated macrophages. C57BL/6 mice show stronger evidence of macrophage polarization than BALB/c mice, which may contribute to their relative resistance to pathogens. Our computational methods can be generally adopted to uncover biological variation between cell populations.
巨噬细胞是先天免疫系统的重要组成部分,其功能异质性的起源仍存在争议。虽然不同的小鼠品系在免疫反应上存在差异,但它们的预刺激巨噬细胞的基因表达变异范围尚不清楚。我们采用一种新的 scRNA-seq 分析方法,揭示了 BALB/c 和 C57BL/6 小鼠未受刺激的巨噬细胞群体中的基因表达变异。结果表明,在刺激前就可以检测到内在的品系间差异,并且我们将未受刺激的单细胞置于刺激后的巨噬细胞基因表达图谱中。与 BALB/c 小鼠相比,C57BL/6 小鼠表现出更强的巨噬细胞极化证据,这可能有助于它们对病原体的相对抵抗力。我们的计算方法可以普遍用于揭示细胞群体之间的生物学变异。