{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:25:07Z","timestamp":1788265507337,"version":"build-2803163510"},"reference-count":53,"publisher":"The Company of Biologists","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Council","award":["MR\/5036121\/1"],"award-info":[{"award-number":["MR\/5036121\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In Barrett's oesophagus (BO), the precursor of oesophageal adenocarcinoma, the adult stratified squamous epithelium is replaced by a simple columnar phenotype. This has been considered metaplasia, i.e. the inappropriate conversion from one adult cell type to another. Alternatively, BO could represent reversion to an embryonic-fetal state when the early foregut is initially lined by simple columnar epithelium. Exploration of this hypothesis has been hampered by inadequate molecular details of human oesophageal development. Here, we adopted single-cell transcriptomic and epigenomic approaches to discover and de-code the cell types that constitute the initial primitive columnar, transitory and subsequently stratified lower oesophageal epithelium. Each stage comprises several previously undefined epithelial subpopulations. Importantly, early foregut columnar epithelial cells share core regulatory and gene expression programmes with BO. Among these, HNF4A is identified as a prominent transcriptional regulator that forms the core of a regulatory network in early foregut columnar cells. These regulatory networks are also central to programmes known to be reactivated in BO. Collectively, these data argue that the path to BO involves reactivation of pathways that define primitive embryonic and fetal epithelial cell states.<\/jats:p>","DOI":"10.1242\/dev.204735","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T11:19:56Z","timestamp":1763637596000},"source":"Crossref","is-referenced-by-count":1,"title":["Metaplastic Barrett's oesophagus represents reversion to a developmental-like epithelial cell state"],"prefix":"10.1242","volume":"152","author":[{"given":"Syed","family":"Murtuza Baker","sequence":"first","affiliation":[{"name":"Manchester Academic Health Sciences Centre, University of Manchester 1 Faculty of Biology, Medicine & Health , , Oxford Road, Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoibheann","family":"Mullan","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Sciences Centre, University of Manchester 1 Faculty of Biology, Medicine & Health , , Oxford Road, Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Jennings","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Sciences Centre, University of Manchester 1 Faculty of Biology, Medicine & Health , , Oxford Road, Manchester M13 9PT ,","place":["UK"]},{"name":"Manchester University NHS Foundation Trust 2 Endocrinology Department , , Grafton Street, Manchester M13 9WU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Piper Hanley","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Sciences Centre, University of Manchester 1 Faculty of Biology, Medicine & Health , , Oxford Road, Manchester M13 9PT ,","place":["UK"]},{"name":"Wellcome Centre for Cell-Matrix Research, University of Manchester 3 , Oxford Road, Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeng","family":"Ang","sequence":"additional","affiliation":[{"name":"University of Manchester 4 School of Medical Sciences, Faculty of Biology, Medicine and Health , , Oxford Road, Manchester M13 9PT ,","place":["UK"]},{"name":"Salford Royal Hospital, Northen Care Alliance 5 GI Science , , Stott Lane, Salford M6 8HD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Palles","sequence":"additional","affiliation":[{"name":"Department of Cancer and Genomic Sciences, College of Medicine & Health, University of Birmingham 6 , Edgbaston, Birmingham B15 2TT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Sciences Centre, University of Manchester 1 Faculty of Biology, Medicine & Health , , Oxford Road, Manchester M13 9PT ,","place":["UK"]},{"name":"Department of Cancer and Genomic Sciences, College of Medicine & Health, University of Birmingham 6 , Edgbaston, Birmingham B15 2TT ,","place":["UK"]},{"name":"University Hospitals Birmingham NHS Foundation Trust 7 , Birmingham B15 2GW ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7395-9552","authenticated-orcid":false,"given":"Andrew D.","family":"Sharrocks","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Sciences Centre, University of Manchester 1 Faculty of Biology, Medicine & Health , , Oxford Road, Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"2026090108082990300_DEV204735C1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/nbt.4314","article-title":"Dimensionality reduction for visualizing single-cell data using UMAP","volume":"37","author":"Becht","year":"2018","journal-title":"Nat. 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