{"doi":"10.1101/2021.08.05.455152","title":"Cellular heterogeneity and molecular reprogramming of host response during influenza acute lung injury","abstract":"Abstract Acute lung injury (ALI) caused by influenza A virus (IAV or influenza) manifests from dysregulated cellular interactions between hematopoietic and non-hematopoietic cells that develop into a pathologic host response. However, the lung’s diverse cellular framework that dictates the pathologic host response and acute lung injury remains incompletely understood. We performed a single-cell RNA-seq (scRNA-seq) analysis of total lung cells in mice from severe influenza to examine the cellular heterogeneity and cell-specific regulation of host response. We observed that IAV infection resulted in significant myelopoiesis, predominantly monocyte, and macrophage subsets, which constituted over 50% of total immune cells. IAV infection resulted in the significant loss of endothelial and fibroblast cells, representing the most predominant non-hematopoietic cells and crucial to regulating inflammatory response and barrier integrity. We also show the cell-cell communication dynamics of interferon and chemokine signaling and global regulation of these responses in transition from homeostatic to IAV infection state. These data highlight a robust application of scRNA-seq technology in establishing the atlas of cellular heterogeneity from its homeostatic transition to infection state and the host response regulation in IAV-mediated lung pathology.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226031,"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":0.8789,"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":710500,"name":"Dan Justin Kalenda Yombo","orcid":"0000-0002-1469-503X","position":1,"is_corresponding":false},{"id":465946,"name":"Taylor Schmit","orcid":"0000-0002-7637-1110","position":2,"is_corresponding":false},{"id":282912,"name":"Zhihan Wang","orcid":"0000-0002-3617-477X","position":3,"is_corresponding":false},{"id":465947,"name":"Sumit Ghosh","orcid":"0000-0002-6890-954X","position":4,"is_corresponding":false},{"id":829055,"name":"Venkatachelem Sathish","orcid":null,"position":5,"is_corresponding":false},{"id":322588,"name":"Ramkumar Mathur","orcid":"0000-0002-9317-2631","position":6,"is_corresponding":false},{"id":828749,"name":"Min Wu","orcid":"0000-0002-0183-0490","position":7,"is_corresponding":false},{"id":350442,"name":"Junguk Hur","orcid":"0000-0002-0736-2149","position":8,"is_corresponding":false},{"id":465950,"name":"M. Nadeem Khan","orcid":"0000-0001-7870-4989","position":9,"is_corresponding":false},{"id":282916,"name":"Kai Guo","orcid":"0000-0002-4651-781X","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:30.292454Z","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":[]}