» Articles » PMID: 37723145

Whole-genome Screens Reveal Regulators of Differentiation State and Context-dependent Migration in Human Neutrophils

Overview
Journal Nat Commun
Specialty Biology
Date 2023 Sep 18
PMID 37723145
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

A function of TPL/TBL1-type corepressors is to nucleate the assembly of the preinitiation complex.

Leydon A, Downing B, Solano Sanchez J, Loll-Krippleber R, Belliveau N, Rodriguez-Mias R J Cell Biol. 2024; 224(2).

PMID: 39652081 PMC: 11627113. DOI: 10.1083/jcb.202404103.


Galvanin is an electric-field sensor for directed cell migration.

Belliveau N, Footer M, Platenkamp A, Kim H, Eustis T, Theriot J bioRxiv. 2024; .

PMID: 39386424 PMC: 11463530. DOI: 10.1101/2024.09.23.614580.


A conserved function of corepressors is to nucleate assembly of the transcriptional preinitiation complex.

Leydon A, Downing B, Solano Sanchez J, Loll-Krippleber R, Belliveau N, Rodriguez-Mias R bioRxiv. 2024; .

PMID: 38617365 PMC: 11014602. DOI: 10.1101/2024.04.01.587599.


The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb.

Feng R, Liu F, Li R, Zhou Z, Lin Z, Lin S Cell Res. 2024; 34(5):355-369.

PMID: 38448650 PMC: 11061317. DOI: 10.1038/s41422-024-00938-z.


Not all (cells) who wander are lost: Upstream migration as a pervasive mode of amoeboid cell motility.

Buffone Jr A, Hammer D, Kim S, Anderson N, Mochida A, Lee D Front Cell Dev Biol. 2023; 11:1291201.

PMID: 38020916 PMC: 10651737. DOI: 10.3389/fcell.2023.1291201.

References
1.
Gironi B, Kahveci Z, McGill B, Lechner B, Pagliara S, Metz J . Effect of DMSO on the Mechanical and Structural Properties of Model and Biological Membranes. Biophys J. 2020; 119(2):274-286. PMC: 7376087. DOI: 10.1016/j.bpj.2020.05.037. View

2.
Gao R, Zhao S, Jiang X, Sun Y, Zhao S, Gao J . A large-scale screen reveals genes that mediate electrotaxis in Dictyostelium discoideum. Sci Signal. 2015; 8(378):ra50. PMC: 4470479. DOI: 10.1126/scisignal.aab0562. View

3.
Morgens D, Deans R, Li A, Bassik M . Systematic comparison of CRISPR/Cas9 and RNAi screens for essential genes. Nat Biotechnol. 2016; 34(6):634-6. PMC: 4900911. DOI: 10.1038/nbt.3567. View

4.
Spellberg B, Collins M, French S, Edwards Jr J, Fu Y, Ibrahim A . A phagocytic cell line markedly improves survival of infected neutropenic mice. J Leukoc Biol. 2005; 78(2):338-44. DOI: 10.1189/jlb.0205072. View

5.
Haney M, Bohlen C, Morgens D, Ousey J, Barkal A, Tsui C . Identification of phagocytosis regulators using magnetic genome-wide CRISPR screens. Nat Genet. 2018; 50(12):1716-1727. PMC: 6719718. DOI: 10.1038/s41588-018-0254-1. View