{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:42:17Z","timestamp":1787586137180,"version":"build-2736575974"},"posted":{"date-parts":[[2023,1,26]]},"group-title":"Genomics","reference-count":55,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Barrett\u2019s esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett\u2019s esophagus have not been resolved in humans. To address this, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis revealed discrete lineages in Barrett\u2019s esophagus, normal esophagus, and gastric cardia. Transitional basal progenitor cells of the gastroesophageal junction were unexpectedly related to both esophagus and gastric cardia cells. Barrett\u2019s esophagus was polyclonal, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic foci were initiated by the expansion of a single molecularly aberrant Barrett\u2019s esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett\u2019s esophagus, linking cell states along the full disease trajectory, from its origin to cancer.<\/jats:p>","DOI":"10.1101\/2023.01.26.525564","type":"posted-content","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T22:25:13Z","timestamp":1674771913000},"source":"Crossref","is-referenced-by-count":10,"title":["Clonal cell states link Barrett\u2019s esophagus and esophageal adenocarcinoma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2593-2798","authenticated-orcid":false,"given":"Rodrigo A.","family":"Gier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-051X","authenticated-orcid":false,"given":"Ra\u00fal A. Reyes","family":"Hueros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7884-5973","authenticated-orcid":false,"given":"Jiazhen","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"DeMarshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-2804","authenticated-orcid":false,"given":"Tatiana A.","family":"Karakasheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-7063","authenticated-orcid":false,"given":"Amanda B.","family":"Muir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Falk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0880-5749","authenticated-orcid":false,"given":"Nancy R.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3539-9886","authenticated-orcid":false,"given":"Sydney M.","family":"Shaffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023020809350619000_2023.01.26.525564v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.68"},{"key":"2023020809350619000_2023.01.26.525564v2.2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41572-019-0086-z","article-title":"Barrett oesophagus","volume":"5","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2023020809350619000_2023.01.26.525564v2.3","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1053\/j.gastro.2019.03.072","article-title":"Pathogenesis and Cells of Origin of Barrett\u2019s Esophagus","volume":"157","year":"2019","journal-title":"Gastroenterology"},{"key":"2023020809350619000_2023.01.26.525564v2.4","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1053\/j.gastro.2021.12.271","article-title":"Clonal Transitions and Phenotypic Evolution in Barrett\u2019s Esophagus","volume":"162","year":"2022","journal-title":"Gastroenterology"},{"key":"2023020809350619000_2023.01.26.525564v2.5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41575-021-00531-4","article-title":"Evolutionary dynamics in Barrett oesophagus: implications for surveillance, risk stratification and therapy","volume":"19","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2023020809350619000_2023.01.26.525564v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00400-x"},{"key":"2023020809350619000_2023.01.26.525564v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.12.004"},{"key":"2023020809350619000_2023.01.26.525564v2.8","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/j.stem.2021.03.019","article-title":"Reactivation of the Hedgehog pathway in esophageal progenitors turns on an embryonic-like program to initiate columnar metaplasia","volume":"28","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2023020809350619000_2023.01.26.525564v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.05.026"},{"key":"2023020809350619000_2023.01.26.525564v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature24269"},{"key":"2023020809350619000_2023.01.26.525564v2.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd1449"},{"key":"2023020809350619000_2023.01.26.525564v2.12","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.143339"},{"key":"2023020809350619000_2023.01.26.525564v2.13","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301174"},{"key":"2023020809350619000_2023.01.26.525564v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3013"},{"key":"2023020809350619000_2023.01.26.525564v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3343"},{"key":"2023020809350619000_2023.01.26.525564v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3357"},{"key":"2023020809350619000_2023.01.26.525564v2.17","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1038\/s41591-020-1033-y","article-title":"Genomic copy number predicts esophageal cancer years before transformation","volume":"26","year":"2020","journal-title":"Nat. Med."},{"key":"2023020809350619000_2023.01.26.525564v2.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1907-7"},{"key":"2023020809350619000_2023.01.26.525564v2.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.022"},{"key":"2023020809350619000_2023.01.26.525564v2.20","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1038\/s41587-022-01210-8","article-title":"Mitochondrial variant enrichment from high-throughput single-cell RNA sequencing resolves clonal populations","volume":"40","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"2023020809350619000_2023.01.26.525564v2.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.05.012"},{"key":"2023020809350619000_2023.01.26.525564v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06796-9"},{"key":"2023020809350619000_2023.01.26.525564v2.23","doi-asserted-by":"publisher","DOI":"10.1002\/stem.67"},{"key":"2023020809350619000_2023.01.26.525564v2.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02621-x"},{"key":"2023020809350619000_2023.01.26.525564v2.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03852-1"},{"key":"2023020809350619000_2023.01.26.525564v2.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2922-4"},{"key":"2023020809350619000_2023.01.26.525564v2.27","doi-asserted-by":"crossref","unstructured":"Choi, H. M. T. et al. Third-generation in situ hybridization chain reaction: multiplexed, quantitative, sensitive, versatile, robust. Development 145, (2018).","DOI":"10.1242\/dev.165753"},{"key":"2023020809350619000_2023.01.26.525564v2.28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.7.915"},{"key":"2023020809350619000_2023.01.26.525564v2.29","doi-asserted-by":"crossref","first-page":"5912","DOI":"10.1038\/s41467-020-19691-z","article-title":"FAM3D is essential for colon homeostasis and host defense against inflammation associated carcinogenesis","volume":"11","year":"2020","journal-title":"Nat. Commun."},{"key":"2023020809350619000_2023.01.26.525564v2.30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2050.2009.00979.x"},{"key":"2023020809350619000_2023.01.26.525564v2.31","first-page":"e00272","article-title":"LGR5 in Barrett\u2019s Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia","volume":"12","year":"2020","journal-title":"Clin. Transl. Gastroenterol."},{"key":"2023020809350619000_2023.01.26.525564v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00180-6"},{"key":"2023020809350619000_2023.01.26.525564v2.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.04.018"},{"key":"2023020809350619000_2023.01.26.525564v2.34","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.stemcr.2017.01.006","article-title":"SHISA6 Confers Resistance to Differentiation-Promoting Wnt\/\u03b2-Catenin Signaling in Mouse Spermatogenic Stem Cells","volume":"8","year":"2017","journal-title":"Stem Cell Reports"},{"key":"2023020809350619000_2023.01.26.525564v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/34848"},{"key":"2023020809350619000_2023.01.26.525564v2.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1085-7"},{"key":"2023020809350619000_2023.01.26.525564v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2591"},{"key":"2023020809350619000_2023.01.26.525564v2.38","doi-asserted-by":"publisher","DOI":"10.1038\/nature20805"},{"key":"2023020809350619000_2023.01.26.525564v2.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03525-z"},{"key":"2023020809350619000_2023.01.26.525564v2.40","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1038\/s41467-021-23949-5","article-title":"Single cell derived mRNA signals across human kidney tumors","volume":"12","year":"2021","journal-title":"Nat. Commun."},{"key":"2023020809350619000_2023.01.26.525564v2.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2014.10.005"},{"key":"2023020809350619000_2023.01.26.525564v2.42","doi-asserted-by":"crossref","unstructured":"Reznik, E. et al. Mitochondrial DNA copy number variation across human cancers. Elife 5, (2016).","DOI":"10.7554\/eLife.10769"},{"key":"2023020809350619000_2023.01.26.525564v2.43","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41587-021-00837-3","article-title":"Variability within rare cell states enables multiple paths toward drug resistance","volume":"39","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"2023020809350619000_2023.01.26.525564v2.44","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.05.442755"},{"key":"2023020809350619000_2023.01.26.525564v2.45","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.04.048"},{"key":"2023020809350619000_2023.01.26.525564v2.46","doi-asserted-by":"crossref","first-page":"979","DOI":"10.12688\/f1000research.73600.1","article-title":"Doublet identification in single-cell sequencing data using scDblFinder","volume":"10","year":"2021","journal-title":"F1000Res."},{"key":"2023020809350619000_2023.01.26.525564v2.47","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","year":"2019","journal-title":"Nat. Methods"},{"key":"2023020809350619000_2023.01.26.525564v2.48","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0249"},{"key":"2023020809350619000_2023.01.26.525564v2.49","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2023020809350619000_2023.01.26.525564v2.50","doi-asserted-by":"crossref","first-page":"e0375121","DOI":"10.1128\/mbio.03751-21","article-title":"Subcellular Detection of SARS-CoV-2 RNA in Human Tissue Reveals Distinct Localization in Alveolar Type 2 Pneumocytes and Alveolar Macrophages","volume":"13","year":"2022","journal-title":"MBio"},{"key":"2023020809350619000_2023.01.26.525564v2.51","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"2023020809350619000_2023.01.26.525564v2.52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004873"},{"key":"2023020809350619000_2023.01.26.525564v2.53","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl646"},{"key":"2023020809350619000_2023.01.26.525564v2.54","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000919"},{"key":"2023020809350619000_2023.01.26.525564v2.55","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S51484"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.01.26.525564","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:11:32Z","timestamp":1768450292000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.01.26.525564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":55,"URL":"https:\/\/doi.org\/10.1101\/2023.01.26.525564","relation":{},"subject":[],"published":{"date-parts":[[2023,1,26]]},"subtype":"preprint"}}