{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:31:43Z","timestamp":1792787503364,"version":"4.5.0"},"reference-count":29,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Child Health Research Appeal Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2017,2,1]]},"abstract":"<jats:p>Air-liquid interface (ALI) culture of primary airway epithelial cells enables mucociliary differentiation providing an in vitro model of the human airway, but their proliferative potential is limited. To extend proliferation, these cells were previously transduced with viral oncogenes or mouse Bmi-1 + hTERT, but the resultant cell lines did not undergo mucociliary differentiation. We hypothesized that use of human BMI-1 alone would increase the proliferative potential of bronchial epithelial cells while retaining their mucociliary differentiation potential. Cystic fibrosis (CF) and non-CF bronchial epithelial cells were transduced by lentivirus with BMI-1 and then their morphology, replication kinetics, and karyotype were assessed. When differentiated at ALI, mucin production, ciliary function, and transepithelial electrophysiology were measured. Finally, shRNA knockdown of DNAH5 in BMI-1 cells was used to model primary ciliary dyskinesia (PCD). BMI-1-transduced basal cells showed normal cell morphology, karyotype, and doubling times despite extensive passaging. The cell lines underwent mucociliary differentiation when cultured at ALI with abundant ciliation and production of the gel-forming mucins MUC5AC and MUC5B evident. Cilia displayed a normal beat frequency and 9+2 ultrastructure. Electrophysiological characteristics of BMI-1-transduced cells were similar to those of untransduced cells. shRNA knockdown of DNAH5 in BMI-1 cells produced immotile cilia and absence of DNAH5 in the ciliary axoneme as seen in cells from patients with PCD. BMI-1 delayed senescence in bronchial epithelial cells, increasing their proliferative potential but maintaining mucociliary differentiation at ALI. We have shown these cells are amenable to genetic manipulation and can be used to produce novel disease models for research and dissemination.<\/jats:p>","DOI":"10.1152\/ajplung.00471.2016","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T22:15:56Z","timestamp":1481840156000},"page":"L258-L267","source":"Crossref","is-referenced-by-count":49,"title":["BMI-1 extends proliferative potential of human bronchial epithelial cells while retaining their mucociliary differentiation capacity"],"prefix":"10.1152","volume":"312","author":[{"given":"Mustafa M.","family":"Munye","sequence":"first","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Shoemark","sequence":"additional","affiliation":[{"name":"Imperial College London, UK Electron Microscopy Department, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Hirst","sequence":"additional","affiliation":[{"name":"Primary Ciliary Dyskinesia Centre Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette M.","family":"Delhove","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyson V.","family":"Sharp","sequence":"additional","affiliation":[{"name":"Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan R.","family":"McKay","sequence":"additional","affiliation":[{"name":"School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"O\u2019Callaghan","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"Baines","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, St George's, University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Howe","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Hart","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.04.035"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201507-1414OC"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950019165"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.10.1.7507342"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90314.2008"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-0175"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072299"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059436"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0046TE"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200601-084OC"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.6b03013"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/16476"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90388.2008"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005821"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.10.036"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2011.04.005"},{"key":"B18","first-page":"7147","volume":"63","author":"Milyavsky M","year":"2003","journal-title":"Cancer Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0274MA"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1089\/153685903322538818"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-2913"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/2046-2530-1-14"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00205312"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213241109"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12847"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149550"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2328"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s40139-013-0016-9"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707343"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00471.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T01:46:52Z","timestamp":1567993612000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00471.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,1]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2,1]]}},"alternative-id":["10.1152\/ajplung.00471.2016"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00471.2016","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,1]]}}}