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Here, we explore the heterogeneity of these cells, with respect to expression of the cystic fibrosis transmembrane conductance regulator (CFTR) transcript and protein. We isolate clones of 16HBE14o<jats:sup>\u2212<\/jats:sup> with stably higher and lower levels of CFTR in comparison to bulk 16HBE14o<jats:sup>\u2212<\/jats:sup>, designated CFTR<jats:sup>high<\/jats:sup> and CFTR<jats:sup>low<\/jats:sup>. Detailed characterization of the <jats:italic>CFTR<\/jats:italic> locus in these clones by ATAC\u2010seq and 4C\u2010seq showed open chromatin profiles and higher order chromatin structure that correlate with <jats:italic>CFTR<\/jats:italic> expression levels. Transcriptomic profiling of CFTR<jats:sup>high<\/jats:sup> and CFTR<jats:sup>low<\/jats:sup> cells showed that the CFTR<jats:sup>high<\/jats:sup> cells had an elevated inflammatory\/innate immune response phenotype. These results encourage caution in interpreting functional data from clonal lines of 16HBE14o<jats:sup>\u2212<\/jats:sup> cells, generated after genomic or other manipulations.<\/jats:p>","DOI":"10.14814\/phy2.15700","type":"journal-article","created":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T07:10:29Z","timestamp":1685776229000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cellular heterogeneity in the <scp>16HBE14o<\/scp><sup>\u2212<\/sup> airway epithelial line impacts biological readouts"],"prefix":"10.14814","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1980-2543","authenticated-orcid":false,"given":"Jenny L.","family":"Kerschner","sequence":"first","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4069-1761","authenticated-orcid":false,"given":"Alekh","family":"Paranjapye","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-2546","authenticated-orcid":false,"given":"Ann","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0161072"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/EPI.28967\/SUPPL_FILE\/KEPI_A_10928967_SM0001.ZIP"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070429"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270227"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20201532\/226530"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCF.2015.03.003"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/THORAXJNL\u20102013\u2010203204"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4396"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/AJRCMB.10.1.7507342"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.OMTM.2020.05.002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0123520"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1461\u20105347(99)00231\u2010X"},{"key":"e_1_2_11_15_1","first-page":"457","article-title":"Deletion mapping of DNA regions required for SV40 early region promoter function in vivo","volume":"1","author":"Fromm M.","year":"1982","journal-title":"Journal of Molecular and Applied Genetics"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/GENES6030543"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00193810"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/DVDY.293"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-022-00378-7"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.OMTN.2022.04.033"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YMETH.2019.07.014"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02634315"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00255.2002"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTT656"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_11_26_1","first-page":"3215","article-title":"Cytogenetic instability with balanced chromosome changes in an SV40 transformed human uroepithelial cell line","volume":"48","author":"Meisner L. 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