{"doi":"10.1126/sciadv.aba7702","title":"Harnessing lipid signaling pathways to target specialized pro-angiogenic neutrophil subsets for regenerative immunotherapy","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":"Science Advances","year":2020,"id":103534,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":504417,"name":"Caitlin Sok","orcid":"0009-0006-8747-6125","position":1,"is_corresponding":false},{"id":400466,"name":"Lauren A. Hymel","orcid":"0000-0002-6749-8486","position":2,"is_corresponding":false},{"id":505482,"name":"FredE. Pittman","orcid":null,"position":3,"is_corresponding":false},{"id":401266,"name":"William Y. York","orcid":null,"position":4,"is_corresponding":false},{"id":504418,"name":"Quoc D. Mac","orcid":"0000-0003-2745-4734","position":5,"is_corresponding":false},{"id":504419,"name":"Sofiya Vyshnya","orcid":"0000-0001-8713-9803","position":6,"is_corresponding":false},{"id":294505,"name":"Hong Seo Lim","orcid":"0000-0002-3641-231X","position":7,"is_corresponding":false},{"id":497869,"name":"Gabriel A. Kwong","orcid":"0000-0002-6255-6755","position":8,"is_corresponding":false},{"id":294506,"name":"Peng Qiu","orcid":"0000-0003-3256-0734","position":9,"is_corresponding":false},{"id":245035,"name":"Edward A. Botchwey","orcid":"0000-0003-1140-5786","position":10,"is_corresponding":false},{"id":400469,"name":"T. Turner","orcid":"0000-0003-3708-9072","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T22:42:48.999009Z","pmid":"33127670","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}