{"doi":"10.1172/jci.insight.158937","title":"Culture impact on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells","abstract":"Dysfunction of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, is implicated in pulmonary disease pathogenesis, highlighting the importance of human in vitro models. However, AEC2-like cells in culture have yet to be directly compared to their in vivo counterparts at single-cell resolution. Here, we performed head-to-head comparisons among the transcriptomes of primary (1°) adult human AEC2s, their cultured progeny, and human induced pluripotent stem cell-derived AEC2s (iAEC2s). We found each population occupied a distinct transcriptomic space with cultured AEC2s (1° and iAEC2s) exhibiting similarities to and differences from freshly purified 1° cells. Across each cell type, we found an inverse relationship between proliferative and maturation states, with preculture 1° AEC2s being most quiescent/mature and iAEC2s being most proliferative/least mature. Cultures of either type of human AEC2s did not generate detectable alveolar type 1 cells in these defined conditions; however, a subset of iAEC2s cocultured with fibroblasts acquired a transitional cell state described in mice and humans to arise during fibrosis or following injury. Hence, we provide direct comparisons of the transcriptomic programs of 1° and engineered AEC2s, 2 in vitro models that can be harnessed to study human lung health and disease.","journal":"JCI Insight","year":2022,"id":240101,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":617302,"name":"Carolina Garcia-de-Alba","orcid":null,"position":1,"is_corresponding":false},{"id":230900,"name":"Changfu Yao","orcid":"0000-0003-1357-5017","position":2,"is_corresponding":false},{"id":317630,"name":"Patrizia Pessina","orcid":"0000-0002-4227-411X","position":3,"is_corresponding":false},{"id":232288,"name":"Jessie Huang","orcid":"0000-0002-5297-3563","position":4,"is_corresponding":false},{"id":89670,"name":"Carlos Villacorta-Martín","orcid":"0000-0002-1350-465X","position":5,"is_corresponding":false},{"id":634477,"name":"Olivia T. Hix","orcid":"0000-0001-8870-5571","position":6,"is_corresponding":false},{"id":579037,"name":"Kasey Minakin","orcid":null,"position":7,"is_corresponding":false},{"id":790268,"name":"Claire L. Burgess","orcid":"0000-0001-9609-8839","position":8,"is_corresponding":false},{"id":260367,"name":"Pushpinder Bawa","orcid":"0000-0002-8370-3638","position":9,"is_corresponding":false},{"id":867181,"name":"Aditi Murthy","orcid":"0009-0004-6983-4836","position":10,"is_corresponding":false},{"id":284478,"name":"Bindu Konda","orcid":"0000-0001-5949-922X","position":11,"is_corresponding":false},{"id":235950,"name":"Michael F. Beers","orcid":"0000-0002-2149-3209","position":12,"is_corresponding":false},{"id":230901,"name":"Barry R. Stripp","orcid":"0000-0003-4348-2137","position":13,"is_corresponding":false},{"id":28706,"name":"Carla F. Kim","orcid":"0000-0002-2366-9538","position":14,"is_corresponding":false},{"id":228731,"name":"Darrell N. Kotton","orcid":"0000-0002-9604-8476","position":15,"is_corresponding":false},{"id":275576,"name":"Konstantinos–Dionysios Alysandratos","orcid":"0000-0002-5611-0343","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T00:22:46.554789Z","pmid":"36454643","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":[]}