{"doi":"10.1016/j.celrep.2020.107872","title":"Single-Cell and Population Transcriptomics Reveal Pan-epithelial Remodeling in Type 2-High Asthma","abstract":"The type 2 cytokine-high asthma endotype (T2H) is characterized by IL-13-driven mucus obstruction of the airways. To further investigate this incompletely understood pathobiology, we characterize IL-13 effects on human airway epithelial cell cultures using single-cell RNA sequencing, finding that IL-13 generates a distinctive transcriptional state for each cell type. Specifically, we discover a mucus secretory program induced by IL-13 in all cell types which converts both mucus and defense secretory cells into a metaplastic state with emergent mucin production and secretion, while leading to ER stress and cell death in ciliated cells. The IL-13-remodeled epithelium secretes a pathologic, mucin-imbalanced, and innate immunity-depleted proteome that arrests mucociliary motion. Signatures of IL-13-induced cellular remodeling are mirrored by transcriptional signatures characteristic of the nasal airway epithelium within T2H versus T2-low asthmatic children. Our results reveal the epithelium-wide scope of T2H asthma and present candidate therapeutic targets for restoring normal epithelial function.","journal":"Cell Reports","year":2020,"id":51123,"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":167,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"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":240436,"name":"Jamie L. Everman","orcid":"0000-0002-1935-4672","position":1,"is_corresponding":false},{"id":254380,"name":"Maurizio Chioccioli","orcid":"0000-0003-2114-1825","position":2,"is_corresponding":false},{"id":254381,"name":"Luigi Feriani","orcid":"0000-0001-6349-7833","position":3,"is_corresponding":false},{"id":240431,"name":"Katherine C. Goldfarbmuren","orcid":"0000-0001-8774-7454","position":4,"is_corresponding":false},{"id":240432,"name":"Satria P. Sajuthi","orcid":"0000-0001-9598-7298","position":5,"is_corresponding":false},{"id":243588,"name":"Cydney Rios","orcid":null,"position":6,"is_corresponding":false},{"id":254382,"name":"Roger Powell","orcid":"0000-0001-7483-0611","position":7,"is_corresponding":false},{"id":115048,"name":"Michael Armstrong","orcid":null,"position":8,"is_corresponding":false},{"id":256906,"name":"Joe Gomez","orcid":null,"position":9,"is_corresponding":false},{"id":254383,"name":"Cole R. Michel","orcid":"0000-0002-9058-7495","position":10,"is_corresponding":false},{"id":54980,"name":"Celeste Eng","orcid":"0000-0001-7968-1862","position":11,"is_corresponding":false},{"id":88940,"name":"Sam S. Oh","orcid":"0000-0002-2815-6037","position":12,"is_corresponding":false},{"id":248811,"name":"José Rodríguez‐Santana","orcid":null,"position":13,"is_corresponding":false},{"id":254384,"name":"Pietro Cicuta","orcid":"0000-0002-9193-8496","position":14,"is_corresponding":false},{"id":254385,"name":"Nichole Reisdorph","orcid":"0000-0002-0425-8012","position":15,"is_corresponding":false},{"id":24949,"name":"Esteban G. Burchard","orcid":"0000-0001-7475-2035","position":16,"is_corresponding":false},{"id":12167,"name":"Max A. Seibold","orcid":"0000-0002-8685-4263","position":17,"is_corresponding":false},{"id":12143,"name":"Nathan D. Jackson","orcid":"0009-0008-2675-021X","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T20:40:28.278215Z","pmid":"32640237","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":[]}