{"doi":"10.1101/2021.09.28.462132","title":"An anti-inflammatory activation sequence governs macrophage transcriptional dynamics during tissue injury","abstract":"Abstract Macrophages are essential for tissue repair and regeneration. Yet, the molecular programs, as well as the timing of their activation during and after tissue injury are poorly defined. Using a high spatio-temporal resolution single cell analysis of macrophages coupled with live imaging after sensory hair cell death in zebrafish, we find that the same population of macrophages transitions through a sequence of three major anti-inflammatory activation states. Macrophages first show a signature of glucocorticoid activation, then IL10 signaling and finally the induction of oxidative phosphorylation by IL4/Polyamine signaling. Importantly, loss-of-function of glucocorticoid and IL10 signaling shows that each step of the sequence is independently activated. Our results provide the first evidence that macrophages, in addition to a switch from M1 to M2, sequentially and independently transition though three anti-inflammatory pathways in vivo during tissue injury in a regenerating organ. One-Sentence Summary We show that macrophages are sequentially activated by three different anti-inflammatory pathways during tissue injury.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221807,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":814534,"name":"Nhung T. T. Tran","orcid":"0000-0002-9660-8904","position":1,"is_corresponding":false},{"id":822355,"name":"Madeleine E. Swall","orcid":"0000-0001-9028-3056","position":2,"is_corresponding":false},{"id":814535,"name":"Daniel C. Diaz","orcid":"0000-0002-5582-4686","position":3,"is_corresponding":false},{"id":472220,"name":"Jillian F Blanck","orcid":null,"position":4,"is_corresponding":false},{"id":664909,"name":"Tatjana Piotrowski","orcid":"0000-0001-8098-2574","position":5,"is_corresponding":false},{"id":687047,"name":"Nicolas Denans","orcid":"0000-0002-1875-0841","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","pmid":null,"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":[]}