{"doi":"10.1016/j.celrep.2025.115842","title":"Lysophosphatidic acid and sphingosine-1-phosphate are apical polarity cues in multiple organoid systems","abstract":"Apicobasal polarization is crucial for tissue organization during in vivo development and in human organoid models. Extracellular matrix (ECM) signaling typically provides a basal cue, and intestinal and lung organoids reverse polarity from apical-in to apical-out after ECM removal. However, ECM-free brain organoids maintain apical-in polarity, suggesting that media components may influence polarity. Exposing brain organoids to serum induced apical-out orientation. Lysophosphatidic acid (LPA), present in the medium of prior apical-out techniques, was identified as the causative factor. LPA-induced apical-out orientation in brain organoids occurred within 1 day, lasted at least 1 month, and was optimal at human cerebrospinal fluid LPA concentrations. Sphingosine-1-phosphate (S1P) induced similar apical-out polarization. Pharmacological studies revealed that LPA/S1P act via a G-protein coupled receptor/RhoA pathway. Finally, LPA induced apical-out polarity in patient-derived human lung and intestinal organoids, iPSC spheres, and multilineage iPSC-derived intestinal organoids. These findings indicate that LPA signaling is a critical apical polarity cue in multiple tissues.","journal":"Cell Reports","year":2025,"id":525958,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255146,"name":"Jinghui Luo","orcid":"0000-0002-7014-8153","position":1,"is_corresponding":false},{"id":287508,"name":"J. Clayton Walker","orcid":null,"position":2,"is_corresponding":false},{"id":1401477,"name":"Charlotte Y. Yang","orcid":null,"position":3,"is_corresponding":false},{"id":1401478,"name":"Keithan Lee","orcid":null,"position":4,"is_corresponding":false},{"id":1223430,"name":"Ryan C. Spencer","orcid":null,"position":5,"is_corresponding":false},{"id":1401479,"name":"Carissa Matthews","orcid":null,"position":6,"is_corresponding":false},{"id":1401480,"name":"Geshan Feng","orcid":null,"position":7,"is_corresponding":false},{"id":35928,"name":"Peggy P. Hsu","orcid":"0000-0003-1140-2454","position":8,"is_corresponding":false},{"id":989016,"name":"Yusoo Lee","orcid":null,"position":9,"is_corresponding":false},{"id":1401481,"name":"Jack Morgan","orcid":null,"position":10,"is_corresponding":false},{"id":555845,"name":"Charlie J. Childs","orcid":"0000-0002-4480-2625","position":11,"is_corresponding":false},{"id":859288,"name":"Madeline K. Eiken","orcid":"0000-0002-2162-7422","position":12,"is_corresponding":false},{"id":318755,"name":"Katherine D. Walton","orcid":"0000-0001-9108-5617","position":13,"is_corresponding":false},{"id":28520,"name":"Jason R. Spence","orcid":"0000-0001-7869-3992","position":14,"is_corresponding":false},{"id":286742,"name":"Andrew M. Tidball","orcid":"0000-0002-1666-4106","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:25.860105Z","pmid":"40503936","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":[]}