Whole-genome screens reveal regulators of differentiation state and context-dependent migration in human neutrophils

全基因组筛选揭示人类中性粒细胞分化状态和环境依赖性迁移的调控因子

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作者:Nathan M Belliveau ,Matthew J Footer ,Emel Akdoǧan ,Aaron P van Loon ,Sean R Collins ,Julie A Theriot

Abstract

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.

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