{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:41:15Z","timestamp":1784907675416,"version":"3.55.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["IH001"],"award-info":[{"award-number":["IH001"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC 016"],"award-info":[{"award-number":["SRC 016"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC 016"],"award-info":[{"award-number":["SRC 016"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["VIA 028"],"award-info":[{"award-number":["VIA 028"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC 021"],"award-info":[{"award-number":["SRC 021"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC 021"],"award-info":[{"award-number":["SRC 021"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["IH001"],"award-info":[{"award-number":["IH001"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["VIA 028"],"award-info":[{"award-number":["VIA 028"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC 016"],"award-info":[{"award-number":["SRC 016"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Core Support Grant 203151\/Z\/16\/Z"],"award-info":[{"award-number":["Core Support Grant 203151\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Core Support Grant 203151\/Z\/16\/Z"],"award-info":[{"award-number":["Core Support Grant 203151\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Core Support Grant 203151\/Z\/16\/Z"],"award-info":[{"award-number":["Core Support Grant 203151\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Core Support Grant 203151\/Z\/16\/Z"],"award-info":[{"award-number":["Core Support Grant 203151\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Core Support Grant MC_PC_17230"],"award-info":[{"award-number":["Core Support Grant MC_PC_17230"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Core Support Grant MC_PC_17230"],"award-info":[{"award-number":["Core Support Grant MC_PC_17230"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P009581\/1"],"award-info":[{"award-number":["MR\/P009581\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Core Support Grant MC_PC_17230"],"award-info":[{"award-number":["Core Support Grant MC_PC_17230"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P009581\/1"],"award-info":[{"award-number":["MR\/P009581\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["Core Support Grant MC_PC_17230"],"award-info":[{"award-number":["Core Support Grant MC_PC_17230"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU ITN PhyMot"},{"DOI":"10.13039\/501100000849","name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["Training Fellowship NC\/R001987\/1"],"award-info":[{"award-number":["Training Fellowship NC\/R001987\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000849","name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["Project Grant NC\/S001204\/1"],"award-info":[{"award-number":["Project Grant NC\/S001204\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000849","name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["Project Grant NC\/S001204\/1"],"award-info":[{"award-number":["Project Grant NC\/S001204\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000849","name":"National Centre for the Replacement, Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["Project Grant NC\/S001204\/1"],"award-info":[{"award-number":["Project Grant NC\/S001204\/1"]}],"id":[{"id":"10.13039\/501100000849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009855","name":"Roy Castle Lung Cancer Foundation","doi-asserted-by":"publisher","award":["2015\/10\/McCaughan"],"award-info":[{"award-number":["2015\/10\/McCaughan"]}],"id":[{"id":"10.13039\/100009855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009855","name":"Roy Castle Lung Cancer Foundation","doi-asserted-by":"publisher","award":["2015\/10\/McCaughan"],"award-info":[{"award-number":["2015\/10\/McCaughan"]}],"id":[{"id":"10.13039\/100009855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009855","name":"Roy Castle Lung Cancer Foundation","doi-asserted-by":"publisher","award":["2015\/10\/McCaughan"],"award-info":[{"award-number":["2015\/10\/McCaughan"]}],"id":[{"id":"10.13039\/100009855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["Grant New-Chol ERC: 741707"],"award-info":[{"award-number":["Grant New-Chol ERC: 741707"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels of <jats:italic>CFTR<\/jats:italic> (cystic fibrosis transmembrane conductance regulator), the gene mutated in cystic fibrosis. By providing an infinite source of airway epithelial cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could overcome some challenges of studying ionocytes. However, the production of AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we present a platform to produce hiPSC-derived AECs (hiPSC-AECs) including ionocytes and investigate their role in the airway epithelium.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>hiPSCs were differentiated into lung progenitors, which were expanded as 3D organoids and matured by air-liquid interface culture as polarised hiPSC-AEC epithelia. Using CRISPR\/Cas9 technology, we generated a hiPSCs knockout (KO) for <jats:italic>FOXI1<\/jats:italic>, a transcription factor that is essential for ionocyte specification. Differences between <jats:italic>FOXI1<\/jats:italic> KO hiPSC-AECs and their wild-type (WT) isogenic controls were investigated by assessing gene and protein expression, epithelial composition, cilia coverage and motility, pH and transepithelial barrier properties.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mature hiPSC-AEC epithelia contained basal cells, secretory cells, ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and ionocytes. There was no difference between <jats:italic>FOXI1<\/jats:italic> WT and KO hiPSCs in terms of their capacity to differentiate into airway progenitors. However, <jats:italic>FOXI1<\/jats:italic> KO led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to produce ciliated cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our results suggest that ionocytes could have role beyond transepithelial ion transport by regulating epithelial properties and homeostasis in the airway epithelium.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-024-02800-7","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T14:03:01Z","timestamp":1714053781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In vitro platform to model the function of ionocytes in the human airway epithelium"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7463-1046","authenticated-orcid":false,"given":"Marta","family":"Vil\u00e0-Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2732-8949","authenticated-orcid":false,"given":"Laetitia","family":"Pinte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6331-2034","authenticated-orcid":false,"given":"Ricardo","family":"Fradique","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Causa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen","family":"Kool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-8682","authenticated-orcid":false,"given":"Mayuree","family":"Rodrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-8068","authenticated-orcid":false,"given":"Carola Maria","family":"Morell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4917-0652","authenticated-orcid":false,"given":"Maha","family":"Al-Thani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-0902","authenticated-orcid":false,"given":"Linsey","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-5493","authenticated-orcid":false,"given":"Wenrui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1473-9757","authenticated-orcid":false,"given":"Ruhina","family":"Maeshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8254-376X","authenticated-orcid":false,"given":"Stephen L.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-7524","authenticated-orcid":false,"given":"Frank","family":"McCaughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5051-8201","authenticated-orcid":false,"given":"Alessandra","family":"Granata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5533-9130","authenticated-orcid":false,"given":"David N.","family":"Sheppard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-5659","authenticated-orcid":false,"given":"R. Andres","family":"Floto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7426-3792","authenticated-orcid":false,"given":"Emma L.","family":"Rawlins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9193-8496","authenticated-orcid":false,"given":"Pietro","family":"Cicuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3848-2602","authenticated-orcid":false,"given":"Ludovic","family":"Vallier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"issue":"7718","key":"2800_CR1","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41586-018-0394-6","volume":"560","author":"LW Plasschaert","year":"2018","unstructured":"Plasschaert LW, \u017dilionis R, Choo-Wing R, Savova V, Knehr J, Roma G, et al. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature. 2018;560(7718):377\u201381.","journal-title":"Nature"},{"issue":"7718","key":"2800_CR2","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41586-018-0393-7","volume":"560","author":"DT Montoro","year":"2018","unstructured":"Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018;560(7718):319\u201324.","journal-title":"Nature"},{"issue":"3","key":"2800_CR3","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/ng1192-240","volume":"2","author":"JF Engelhardt","year":"1992","unstructured":"Engelhardt JF, Yankaskas JR, Ernst SA, Yang Y, Marino CR, Boucher RC, et al. Submucosal glands are the predominant site of CFTR expression in the human bronchus. Nat Genet. 1992;2(3):240\u20138.","journal-title":"Nat Genet"},{"issue":"9","key":"2800_CR4","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.3390\/cells9092090","volume":"9","author":"P Scudieri","year":"2020","unstructured":"Scudieri P, Musante I, Venturini A, Guidone D, Genovese M, Cresta F, et al. Ionocytes and CFTR Chloride Channel expression in normal and cystic fibrosis nasal and bronchial epithelial cells. Cells. 2020;9(9):2090.","journal-title":"Cells"},{"issue":"10","key":"2800_CR5","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1164\/rccm.202008-3198OC","volume":"203","author":"K Okuda","year":"2021","unstructured":"Okuda K, Dang H, Kobayashi Y, Carraro G, Nakano S, Chen G, et al. Secretory cells dominate Airway CFTR expression and function in human airway superficial epithelia. Am J Respir Crit Care Med. 2021;203(10):1275\u201389.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"2800_CR6","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1038\/s41467-020-16239-z","volume":"11","author":"KC Goldfarbmuren","year":"2020","unstructured":"Goldfarbmuren KC, Jackson ND, Sajuthi SP, Dyjack N, Li KS, Rios CL, et al. Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium. Nat Commun. 2020;11(1):2485.","journal-title":"Nat Commun"},{"issue":"4","key":"2800_CR7","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1242\/dev.055699","volume":"138","author":"IK Quigley","year":"2011","unstructured":"Quigley IK, Stubbs JL, Kintner C. Specification of ion transport cells in the Xenopus larval skin. Development. 2011;138(4):705\u201314.","journal-title":"Development"},{"issue":"9","key":"2800_CR8","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1164\/rccm.202205-1010LE","volume":"207","author":"R Wang","year":"2023","unstructured":"Wang R, Simone-Roach C, Lindstrom-Vautrin J, Wang F, Rollins S, Bawa PS, et al. De Novo Generation of Pulmonary ionocytes from normal and cystic Fibrosis Human Induced Pluripotent Stem cells. Am J Respir Crit Care Med. 2023;207(9):1249\u201353.","journal-title":"Am J Respir Crit Care Med"},{"issue":"13","key":"2800_CR9","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1242\/dev.034884","volume":"136","author":"PN Tsao","year":"2009","unstructured":"Tsao PN, Vasconcelos M, Izvolsky KI, Qian J, Lu J, Cardoso WV. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development. 2009;136(13):2297\u2013307.","journal-title":"Development"},{"issue":"8","key":"2800_CR10","doi-asserted-by":"publisher","first-page":"104751","DOI":"10.1016\/j.isci.2022.104751","volume":"25","author":"CFH Serra","year":"2022","unstructured":"Serra CFH, Liu H, Qian J, Mori M, Lu J, Cardoso WV. Prominin 1 and Notch regulate ciliary length and dynamics in multiciliated cells of the airway epithelium. iScience. 2022;25(8):104751.","journal-title":"iScience"},{"issue":"6","key":"2800_CR11","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1159\/000514579","volume":"211","author":"P Walentek","year":"2022","unstructured":"Walentek P. Signaling Control of Mucociliary Epithelia: stem cells, cell fates, and the plasticity of cell identity in Development and Disease. Cells Tissues Organs. 2022;211(6):736\u201353.","journal-title":"Cells Tissues Organs"},{"issue":"3","key":"2800_CR12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1165\/rcmb.2022-0280OC","volume":"69","author":"Q Cai","year":"2023","unstructured":"Cai Q, Luo M, Tang Y, Yu M, Yuan F, Gasser GN, et al. Sonic hedgehog signaling is essential for pulmonary ionocyte specification in human and ferret Airway Epithelia. Am J Respir Cell Mol Biol. 2023;69(3):295\u2013309.","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2800_CR13","doi-asserted-by":"crossref","unstructured":"Sato Y, Kim D, Turner MJ, Luo Y, Zaidi SSZ, Thomas DY, et al. Am J Respir Cell Mol Biol. 2023;69(3):281\u201394. https:\/\/doi.org\/101165\/rcmb2022-0241OC. Ionocyte-Specific Regulation of CFTR.","DOI":"10.1165\/rcmb.2022-0241OC"},{"issue":"20","key":"2800_CR14","doi-asserted-by":"publisher","first-page":"e171268","DOI":"10.1172\/JCI171268","volume":"133","author":"L Lei","year":"2023","unstructured":"Lei L, Traore S, Ibarra GSR, Karp PH, Rehman T, Meyerholz DK, et al. CFTR-rich ionocytes mediate chloride absorption across airway epithelia. J Clin Invest. 2023;133(20):e171268.","journal-title":"J Clin Invest"},{"issue":"7980","key":"2800_CR15","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/s41586-023-06549-9","volume":"621","author":"F Yuan","year":"2023","unstructured":"Yuan F, Gasser GN, Lemire E, Montoro DT, Jagadeesh K, Zhang Y, et al. Transgenic ferret models define pulmonary ionocyte diversity and function. Nature. 2023;621(7980):857\u201367.","journal-title":"Nature"},{"issue":"5","key":"2800_CR16","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1002\/cne.21020","volume":"497","author":"MG Jonz","year":"2006","unstructured":"Jonz MG, Nurse CA. Epithelial mitochondria-rich cells and associated innervation in adult and developing zebrafish. J Comp Neurol. 2006;497(5):817\u201332.","journal-title":"J Comp Neurol"},{"issue":"1","key":"2800_CR17","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.stemcr.2015.11.010","volume":"6","author":"S Konishi","year":"2016","unstructured":"Konishi S, Gotoh S, Tateishi K, Yamamoto Y, Korogi Y, Nagasaki T, et al. Directed induction of functional multi-ciliated cells in Proximal Airway Epithelial spheroids from Human pluripotent stem cells. Stem cell Rep. 2016;6(1):18\u201325.","journal-title":"Stem cell Rep"},{"issue":"1","key":"2800_CR18","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.stem.2020.09.017","volume":"28","author":"FJ Hawkins","year":"2021","unstructured":"Hawkins FJ, Suzuki S, Beermann M, Lou, Barill\u00e0 C, Wang R, Villacorta-Martin C, et al. Derivation of Airway basal stem cells from human pluripotent stem cells. Cell Stem Cell. 2021;28(1):79\u2013e958.","journal-title":"Cell Stem Cell"},{"issue":"20","key":"2800_CR19","doi-asserted-by":"publisher","first-page":"dev200693","DOI":"10.1242\/dev.200693","volume":"149","author":"RFC Hein","year":"2022","unstructured":"Hein RFC, Conchola AS, Fine AS, Xiao Z, Frum T, Brastrom LK, et al. Stable iPSC-derived NKX2-1\u2009+\u2009lung bud tip progenitor organoids give rise to airway and alveolar cell types. Development. 2022;149(20):dev200693.","journal-title":"Development"},{"issue":"5","key":"2800_CR20","doi-asserted-by":"publisher","first-page":"101083","DOI":"10.1016\/j.isci.2020.101083","volume":"23","author":"P Hor","year":"2020","unstructured":"Hor P, Punj V, Calvert BA, Castaldi A, Miller AJ, Carraro G, et al. Efficient generation and transcriptomic profiling of human iPSC-Derived pulmonary neuroendocrine cells. iScience. 2020;23(5):101083.","journal-title":"iScience"},{"issue":"7658","key":"2800_CR21","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/nature22403","volume":"546","author":"H Kilpinen","year":"2017","unstructured":"Kilpinen H, Goncalves A, Leha A, Afzal V, Alasoo K, Ashford S, et al. Common genetic variation drives molecular heterogeneity in human iPSCs. Nature. 2017;546(7658):370\u20135.","journal-title":"Nature"},{"issue":"6","key":"2800_CR22","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.stem.2017.03.001","volume":"20","author":"KB McCauley","year":"2017","unstructured":"McCauley KB, Hawkins F, Serra M, Thomas DC, Jacob A, Kotton DN. Efficient derivation of functional human airway epithelium from pluripotent stem cells via temporal regulation of wnt signaling. Cell Stem Cell. 2017;20(6):844\u2013e8576.","journal-title":"Cell Stem Cell"},{"issue":"5","key":"2800_CR23","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1182\/blood-2005-02-0516","volume":"106","author":"F Ishikawa","year":"2005","unstructured":"Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, et al. Development of functional human blood and immune systems in NOD\/SCID\/IL2 receptor {gamma} chain(null) mice. Blood. 2005;106(5):1565\u201373.","journal-title":"Blood"},{"issue":"10","key":"2800_CR24","doi-asserted-by":"publisher","first-page":"6477","DOI":"10.4049\/jimmunol.174.10.6477","volume":"174","author":"LD Shultz","year":"2005","unstructured":"Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, et al. Human lymphoid and Myeloid Cell Development in NOD\/LtSz-scid IL2R\u03b3null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174(10):6477\u201389.","journal-title":"J Immunol"},{"issue":"5","key":"2800_CR25","doi-asserted-by":"publisher","first-page":"L1063","DOI":"10.1152\/ajplung.00190.2019","volume":"318","author":"C Leung","year":"2020","unstructured":"Leung C, Wadsworth SJ, Jasemine Yang S, Dorscheid DR. Structural and functional variations in human bronchial epithelial cells cultured in air-liquid interface using different growth media. Am J Physiol - Lung Cell Mol Physiol. 2020;318(5):L1063\u201373.","journal-title":"Am J Physiol - Lung Cell Mol Physiol"},{"issue":"8","key":"2800_CR26","doi-asserted-by":"publisher","first-page":"230185","DOI":"10.1098\/rsos.230185","volume":"10","author":"R Fradique","year":"2023","unstructured":"Fradique R, Causa E, Delahousse C, Kotar J, Pinte L, Vallier L, et al. Assessing motile cilia coverage and beat frequency in mammalian in vitro cell culture tissues. R Soc open Sci. 2023;10(8):230185.","journal-title":"R Soc open Sci"},{"issue":"1","key":"2800_CR27","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.stemcr.2017.11.012","volume":"10","author":"AJ Miller","year":"2018","unstructured":"Miller AJ, Hill DR, Nagy MS, Aoki Y, Dye BR, Chin AM, et al. In Vitro induction and in vivo Engraftment of Lung Bud Tip Progenitor cells derived from human pluripotent stem cells. Stem Cell Rep. 2018;10(1):101\u201319.","journal-title":"Stem Cell Rep"},{"key":"2800_CR28","doi-asserted-by":"publisher","first-page":"121031","DOI":"10.1016\/j.biomaterials.2021.121031","volume":"276","author":"S Ikeo","year":"2021","unstructured":"Ikeo S, Yamamoto Y, Ikeda K, Sone N, Korogi Y, Tomiyama L, et al. Core-shell hydrogel microfiber-expanded pluripotent stem cell-derived lung progenitors applicable to lung reconstruction in vivo. Biomaterials. 2021;276:121031.","journal-title":"Biomaterials"},{"issue":"9","key":"2800_CR29","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/j.stem.2023.07.014","volume":"30","author":"L Ma","year":"2023","unstructured":"Ma L, Thapa BR, Suer JA, Le, Tilston-L\u00fcnel A, Herriges MJ, Berical A, et al. Airway stem cell reconstitution by the transplantation of primary or pluripotent stem cell-derived basal cells. Cell Stem Cell. 2023;30(9):1199\u2013e12617.","journal-title":"Cell Stem Cell"},{"issue":"1","key":"2800_CR30","doi-asserted-by":"publisher","first-page":"3516","DOI":"10.1038\/s41598-023-30603-1","volume":"13","author":"C Pou Casellas","year":"2023","unstructured":"Pou Casellas C, Pleguezuelos-Manzano C, Rookmaaker MB, Verhaar MC, Clevers H. Transcriptomic profile comparison reveals conservation of ionocytes across multiple organs. Sci Rep. 2023;13(1):3516.","journal-title":"Sci Rep"},{"issue":"Pt 8","key":"2800_CR31","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1113\/jphysiol.2009.182246","volume":"588","author":"P LeSimple","year":"2010","unstructured":"LeSimple P, Liao J, Robert R, Gruenert DC, Hanrahan JW. Cystic fibrosis transmembrane conductance regulator trafficking modulates the barrier function of airway epithelial cell monolayers. J Physiol. 2010;588(Pt 8):1195\u2013209.","journal-title":"J Physiol"},{"issue":"8","key":"2800_CR32","doi-asserted-by":"publisher","first-page":"F1176","DOI":"10.1152\/ajprenal.00130.2012","volume":"303","author":"H Li","year":"2012","unstructured":"Li H, Yang W, Mendes F, Amaral MD, Sheppard DN. Impact of the cystic fibrosis mutation F508del-CFTR on renal cyst formation and growth. Am J Physiol Ren Physiol. 2012;303(8):F1176\u201386.","journal-title":"Am J Physiol Ren Physiol"},{"issue":"2","key":"2800_CR33","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1242\/dmm.006494","volume":"4","author":"E Dubaissi","year":"2011","unstructured":"Dubaissi E, Papalopulu N. Embryonic frog epidermis: a model for the study of cell-cell interactions in the development of mucociliary disease. Dis Model Mech. 2011;4(2):179\u201392.","journal-title":"Dis Model Mech"},{"issue":"5964","key":"2800_CR34","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1126\/science.1179802","volume":"327","author":"CM Cruciat","year":"2010","unstructured":"Cruciat CM, Ohkawara B, Acebron SP, Karaulanov E, Reinhard C, Ingelfinger D, et al. Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for wnt signaling. Science. 2010;327(5964):459\u201363.","journal-title":"Science"},{"issue":"5\u20136","key":"2800_CR35","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1159\/000492973","volume":"205","author":"DI Sun","year":"2018","unstructured":"Sun DI, Tasca A, Haas M, Baltazar G, Harland RM, Finkbeiner WE, et al. Na+\/H\u2009+\u2009exchangers are required for development and function of vertebrate mucociliary epithelia. Cells Tissues Organs. 2018;205(5\u20136):279\u201392.","journal-title":"Cells Tissues Organs"},{"issue":"2","key":"2800_CR36","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.ydbio.2015.03.013","volume":"408","author":"P Walentek","year":"2015","unstructured":"Walentek P, Beyer T, Hagenlocher C, M\u00fcller C, Feistel K, Schweickert A, et al. ATP4a is required for development and function of the Xenopus mucociliary epidermis - a potential model to study proton pump inhibitor-associated pneumonia. Dev Biol. 2015;408(2):292\u2013304.","journal-title":"Dev Biol"},{"issue":"5","key":"2800_CR37","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.celrep.2012.03.005","volume":"1","author":"P Walentek","year":"2012","unstructured":"Walentek P, Beyer T, Thumberger T, Schweickert A, Blum M. ATP4a is required for wnt-dependent Foxj1 expression and Leftward Flow in Xenopus Left-Right Development. Cell Rep. 2012;1(5):516\u201327.","journal-title":"Cell Rep"},{"issue":"12","key":"2800_CR38","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1038\/ng.267","volume":"40","author":"JL Stubbs","year":"2008","unstructured":"Stubbs JL, Oishi I, Izpis\u00faa Belmonte JC, Kintner C. The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos. Nat Genet. 2008;40(12):1454\u201360.","journal-title":"Nat Genet"},{"issue":"3","key":"2800_CR39","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1242\/dev.071746","volume":"139","author":"A Caron","year":"2012","unstructured":"Caron A, Xu X, Lin X. Wnt\/\u03b2-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer\u2019s vesicle. Development. 2012;139(3):514\u201324.","journal-title":"Development"},{"issue":"3","key":"2800_CR40","doi-asserted-by":"publisher","first-page":"a002964","DOI":"10.1101\/cshperspect.a002964","volume":"1","author":"EK Vladar","year":"2009","unstructured":"Vladar EK, Antic D, Axelrod JD. Planar Cell Polarity Signaling: the developing cell\u2019s compass. Cold Spring Harb Perspect Biol. 2009;1(3):a002964.","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"5","key":"2800_CR41","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.ceb.2010.07.011","volume":"22","author":"JB Wallingford","year":"2010","unstructured":"Wallingford JB. Planar cell polarity signaling, cilia and polarized ciliary beating. Curr Opin Cell Biol. 2010;22(5):597\u2013604.","journal-title":"Curr Opin Cell Biol"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-024-02800-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-024-02800-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-024-02800-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T14:06:39Z","timestamp":1714053999000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-024-02800-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,25]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2800"],"URL":"https:\/\/doi.org\/10.1186\/s12931-024-02800-7","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,25]]},"assertion":[{"value":"3 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were approved by local ethical review committees and conducted according to Home Office project license PPL PEEE9B8E4 (Emma L. Rawlins, University of Cambridge).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"180"}}