{"doi":"10.1101/2021.05.25.445480","title":"Identifying dysregulated immune cell subsets following critical volumetric muscle loss with pseudo-time trajectories","abstract":"Abstract Volumetric muscle loss (VML) results in permanent functional deficits and remains a substantial regenerative medicine challenge. A coordinated immune response is crucial for timely myofiber regeneration, however the immune response following VML has yet to be fully characterized. Here, we leveraged dimensionality reduction and pseudo-time analysis techniques to elucidate the cellular players underlying a functional or pathological outcome as a result of subcritical or critical VML in the murine quadriceps, respectively. We found that critical VML presented with a sustained presence of M2-like and CD206 hi Ly6C hi ‘hybrid’ macrophages whereas subcritical defects resolved these populations. These macrophage subsets may contribute to fibrogenesis in critical VML, especially in the presence of TGF-β. Furthermore, several T cell populations were significantly elevated in critical VML compared to subcritical injuries. Specifically, there was a significant increase of CD127 + T cells at days 3 and 7, and upregulated CD127 expression may indicate aberrant IL-7 signaling in critical VML. These results demonstrate a dysregulated immune response in critical VML that is unable to resolve the chronic inflammatory state and transition to a pro-regenerative microenvironment. These data provide important insights into potential therapeutic strategies which could reduce the immune cell burden and pro-fibrotic signaling characteristic of VML.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":224434,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"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":400468,"name":"Shannon E. Anderson","orcid":"0000-0002-7438-0814","position":1,"is_corresponding":false},{"id":400469,"name":"T. Turner","orcid":"0000-0003-3708-9072","position":2,"is_corresponding":false},{"id":401266,"name":"William Y. York","orcid":null,"position":3,"is_corresponding":false},{"id":294505,"name":"Hong Seo Lim","orcid":"0000-0002-3641-231X","position":4,"is_corresponding":false},{"id":294506,"name":"Peng Qiu","orcid":"0000-0003-3256-0734","position":5,"is_corresponding":false},{"id":242211,"name":"Young C. Jang","orcid":"0000-0002-9489-2104","position":6,"is_corresponding":false},{"id":284966,"name":"Nick J. Willett","orcid":"0000-0003-3421-2549","position":7,"is_corresponding":false},{"id":245035,"name":"Edward A. Botchwey","orcid":"0000-0003-1140-5786","position":8,"is_corresponding":false},{"id":400466,"name":"Lauren A. Hymel","orcid":"0000-0002-6749-8486","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:54:18.470602Z","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":[]}