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

Author

Listed:
  • Nathan M. Belliveau

    (University of Washington)

  • Matthew J. Footer

    (University of Washington)

  • Emel Akdoǧan

    (University of California, Davis)

  • Aaron P. Loon

    (University of Washington)

  • Sean R. Collins

    (University of California, Davis)

  • Julie A. Theriot

    (University of Washington)

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.

Suggested Citation

  • Nathan M. Belliveau & Matthew J. Footer & Emel Akdoǧan & Aaron P. Loon & Sean R. Collins & Julie A. Theriot, 2023. "Whole-genome screens reveal regulators of differentiation state and context-dependent migration in human neutrophils," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41452-x
    DOI: 10.1038/s41467-023-41452-x
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