Abstract:
:To gain insights into neutrophil heterogeneity dynamics in the context of sterile inflammation and wound healing, we performed a pseudotime analysis of single-cell flow cytometry data using the spanning-tree progression analysis of density-normalized events algorithm. This enables us to view neutrophil transitional subsets along a pseudotime trajectory and identify distinct VEGFR1, VEGFR2, and CXCR4 high-expressing pro-angiogenic neutrophils. While the proresolving lipid mediator aspirin-triggered resolvin D1 (AT-RvD1) has a known ability to limit neutrophil infiltration, our analysis uncovers a mode of action in which AT-RvD1 leads to inflammation resolution through the selective reprogramming toward a therapeutic neutrophil subset. This accumulation leads to enhanced vascular remodeling in the skinfold window chamber and a proregenerative shift in macrophage and dendritic cell phenotype, resulting in improved wound closure after skin transplantation. As the targeting of functional immune subsets becomes the key to regenerative immunotherapies, single-cell pseudotime analysis tools will be vital in this field.
journal_name
Sci Advjournal_title
Science advancesauthors
Turner TC,Sok MCP,Hymel LA,Pittman FS,York WY,Mac QD,Vyshnya S,Lim HS,Kwong GA,Qiu P,Botchwey EAdoi
10.1126/sciadv.aba7702subject
Has Abstractpub_date
2020-10-30 00:00:00issue
44issn
2375-2548pii
6/44/eaba7702journal_volume
6pub_type
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