Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USA.
Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
Nat Commun. 2023 Sep 18;14(1):5770. doi: 10.1038/s41467-023-41452-x.
Neutrophils are the most abundant leukocyte in humans and provide a critical early line of defense as part of our innate immune system. We perform a comprehensive, genome-wide assessment of the molecular factors critical to proliferation, differentiation, and cell migration in a neutrophil-like cell line. Through the development of multiple migration screen strategies, we specifically probe directed (chemotaxis), undirected (chemokinesis), and 3D amoeboid cell migration in these fast-moving cells. We identify a role for mTORC1 signaling in cell differentiation, which influences neutrophil abundance, survival, and migratory behavior. Across our individual migration screens, we identify genes involved in adhesion-dependent and adhesion-independent cell migration, protein trafficking, and regulation of the actomyosin cytoskeleton. This genome-wide screening strategy, therefore, provides an invaluable approach to the study of neutrophils and provides a resource that will inform future studies of cell migration in these and other rapidly migrating cells.
中性粒细胞是人体中最丰富的白细胞，作为先天免疫系统的一部分，提供了至关重要的早期防御。我们对类似于中性粒细胞的细胞系中增殖、分化和细胞迁移至关重要的分子因素进行了全面的全基因组评估。通过开发多种迁移筛选策略，我们特别探测了这些快速移动的细胞中的定向（趋化性）、非定向（趋化运动）和 3D 变形虫样细胞迁移。我们确定了 mTORC1 信号在细胞分化中的作用，这影响中性粒细胞的丰度、存活和迁移行为。在我们的单个迁移筛选中，我们确定了与黏附依赖性和非黏附依赖性细胞迁移、蛋白质运输以及肌动球蛋白细胞骨架调节相关的基因。因此，这种全基因组筛选策略为中性粒细胞的研究提供了宝贵的方法，并为今后在这些和其他快速迁移细胞中研究细胞迁移提供了资源。
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