{"doi":"10.1101/2020.09.04.283408","title":"Airway Basal Cells show a dedifferentiated KRT17 <sup>high</sup> Phenotype and promote Fibrosis in Idiopathic Pulmonary Fibrosis","abstract":"ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study we focus on the profibrotic properties of airway basal cells (ABC) obtained from patients with IPF (IPF-ABC). Single cell RNA sequencing of bronchial brushes revealed extensive reprogramming of IPF-ABC towards a KRT17 high PTEN low dedifferentiated cell type. In the 3D organoid model, compared to ABC obtained from healthy volunteers, IPF-ABC give rise to more bronchospheres, de novo bronchial structures resembling lung developmental processes, induce fibroblast proliferation and extracellular matrix deposition in co-culture. Intratracheal application of IPF-ABC into minimally injured lungs of Rag2 -/- or NRG mice causes severe fibrosis, remodeling of the alveolar compartment, and formation of honeycomb cyst-like structures. Connectivity MAP analysis of scRNA seq of bronchial brushings suggested that gene expression changes in IPF-ABC can be reversed by SRC inhibition. After demonstrating enhanced SRC expression and activity in these cells, and in IPF lungs, we tested the effects of saracatinib, a potent SRC inhibitor previously studied in humans. We demonstrated that saracatinib modified in-vitro and in-vivo the profibrotic changes observed in our 3D culture system and novel mouse xenograft model.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121302,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"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":34716,"name":"Jonas C. Schupp","orcid":"0000-0002-7714-8076","position":1,"is_corresponding":false},{"id":560558,"name":"Linda Plappert","orcid":"0000-0002-4642-383X","position":2,"is_corresponding":false},{"id":560559,"name":"Oliver Terwolbeck","orcid":"0000-0003-4312-0005","position":3,"is_corresponding":false},{"id":560560,"name":"Gian Kayser","orcid":"0000-0002-0587-9742","position":4,"is_corresponding":false},{"id":561250,"name":"Peggy Engelhard","orcid":null,"position":5,"is_corresponding":false},{"id":34734,"name":"Taylor Adams","orcid":"0000-0003-4280-9070","position":6,"is_corresponding":false},{"id":560561,"name":"Robert Zweigerdt","orcid":"0000-0002-4656-0770","position":7,"is_corresponding":false},{"id":560562,"name":"Henning Kempf","orcid":"0000-0003-2790-9137","position":8,"is_corresponding":false},{"id":560563,"name":"Stefan Lienenklaus","orcid":"0000-0003-4790-3445","position":9,"is_corresponding":false},{"id":560564,"name":"Wiebke Garrels","orcid":"0000-0003-0737-1245","position":10,"is_corresponding":false},{"id":215728,"name":"Irina Nazarenko","orcid":"0000-0002-2633-1161","position":11,"is_corresponding":false},{"id":560565,"name":"Danny Jonigk","orcid":"0000-0002-5251-2281","position":12,"is_corresponding":false},{"id":560566,"name":"Małgorzata Wygrecka","orcid":"0000-0002-3656-2932","position":13,"is_corresponding":false},{"id":560567,"name":"Denise Klatt","orcid":"0000-0002-0301-6206","position":14,"is_corresponding":false},{"id":560568,"name":"Axel Schambach","orcid":"0000-0003-2743-0070","position":15,"is_corresponding":false},{"id":12162,"name":"Naftali Kaminski","orcid":"0000-0001-5917-4601","position":16,"is_corresponding":false},{"id":2935,"name":"Antje Prasse","orcid":"0000-0002-7336-7458","position":17,"is_corresponding":false},{"id":561249,"name":"Benedikt Jaeger","orcid":null,"position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:14:42.734024Z","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":[]}