{"doi":"10.1016/j.stem.2024.03.017","title":"Generation of human alveolar epithelial type I cells from pluripotent stem cells","abstract":"Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s.","journal":"Cell stem cell","year":2024,"id":417209,"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":77,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232288,"name":"Jessie Huang","orcid":"0000-0002-5297-3563","position":1,"is_corresponding":false},{"id":260367,"name":"Pushpinder Bawa","orcid":"0000-0002-8370-3638","position":2,"is_corresponding":false},{"id":275576,"name":"Konstantinos–Dionysios Alysandratos","orcid":"0000-0002-5611-0343","position":3,"is_corresponding":false},{"id":579037,"name":"Kasey Minakin","orcid":null,"position":4,"is_corresponding":false},{"id":1203466,"name":"Lauren J. Ayers","orcid":null,"position":5,"is_corresponding":false},{"id":239739,"name":"Michael P. Morley","orcid":"0000-0002-0958-7376","position":6,"is_corresponding":false},{"id":239740,"name":"Apoorva Babu","orcid":"0000-0003-3661-5261","position":7,"is_corresponding":false},{"id":89670,"name":"Carlos Villacorta-Martín","orcid":"0000-0002-1350-465X","position":8,"is_corresponding":false},{"id":987305,"name":"Maria Yampolskaya","orcid":"0000-0003-2941-2589","position":9,"is_corresponding":false},{"id":234397,"name":"Anne Hinds","orcid":null,"position":10,"is_corresponding":false},{"id":328225,"name":"Bibek R. Thapa","orcid":"0000-0001-5254-0808","position":11,"is_corresponding":false},{"id":880828,"name":"Feiya Wang","orcid":"0000-0002-7507-6275","position":12,"is_corresponding":false},{"id":650419,"name":"Adeline Matschulat","orcid":"0000-0001-5288-1434","position":13,"is_corresponding":false},{"id":275679,"name":"Pankaj Mehta","orcid":"0000-0003-1290-5897","position":14,"is_corresponding":false},{"id":228733,"name":"Edward E. Morrisey","orcid":"0000-0001-5785-1939","position":15,"is_corresponding":false},{"id":266489,"name":"Xaralabos Varelas","orcid":"0000-0002-2882-4541","position":16,"is_corresponding":false},{"id":228731,"name":"Darrell N. Kotton","orcid":"0000-0002-9604-8476","position":17,"is_corresponding":false},{"id":790268,"name":"Claire L. Burgess","orcid":"0000-0001-9609-8839","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T01:56:50.743370Z","pmid":"38642558","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":[]}