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A phenotypic shift within epithelial cells has been recognised in association with pro-fibrotic signalling. We sought evidence of endocrine cell epithelial-to-mesenchymal transition in CF and non-CF pancreas. Post-mortem pancreatic sections from 24 people with CF and 10 organ donors without CF or diabetes were stained for insulin\/glucagon\/vimentin and Sirius red\/fast green with collagen distribution assessed semi-quantitatively (CF) and quantitatively (non-CF). Analysis of existing single-cell RNA-sequencing datasets (three adult donors without diabetes and nine with chronic pancreatitis) for \u03b1-cell vimentin expression was performed. Cells co-expressing glucagon\/vimentin were detected in a proportion (32(4,61)% (median (Q1,Q3))) of islets in all CF pancreata except donors dying perinatally. CF histopathology was characterised by peri-islet fibrosis, and 60(45,80)% of islets were surrounded by collagen strands. A positive correlation between islet fibrosis and vimentin-expressing \u03b1-cells was seen in non-CF donors &amp;lt;31 years (r = 0.972; P = 0.006). A possible association with donor age was seen in all donors (r = 0.343; P = 0.047). Single-cell RNA-sequencing analysis of isolated islets from non-diabetic donors and donors with chronic pancreatitis confirmed the presence of vimentin-positive and vimentin-negative \u03b1-cells. Differentiated \u03b1-cell function-associated gene expression was maintained. Differentially upregulated processes in co-expressing cells included pathways associated with extracellular matrix organisation, cell\u2013cell adhesion, migratory capability and self-renewal. We have identified and characterised an intermediate epithelial\/mesenchymal state in a sub-population of \u03b1-cells present throughout post-natal life, which may play a role in their response to extrinsic stressors, including fibrosis and ageing.<\/jats:p>","DOI":"10.1530\/joe-24-0190","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T12:50:05Z","timestamp":1737463805000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":6,"title":["Identification of a vimentin-expressing \u03b1-cell phenotype in CF and normal pancreas"],"prefix":"10.1530","volume":"264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-5719","authenticated-orcid":true,"given":"Nicole","family":"Kattner","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University 1 , ,","place":["Newcastle upon Tyne, 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Newcastle University 1 , ,","place":["Newcastle upon Tyne, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung K","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine 2 , , ,","place":["Stanford, California, USA"]},{"name":"Stanford Diabetes Research Centre, Stanford University School of Medicine 3 , , ,","place":["Stanford, California, USA"]},{"name":"Department of Medicine (Endocrinology Division), Stanford University School of Medicine 7 , , ,","place":["Stanford, California, USA"]},{"name":"Department of Pediatrics (Endocrinology Division), Stanford University School of Medicine 8 , , ,","place":["Stanford, California, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Tiniakos","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University 1 , ,","place":["Newcastle upon Tyne, UK"]},{"name":"Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens 9 , ,","place":["Athens, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Kl\u00f6ppel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Technical University of Munich 10 , ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J","family":"Richardson","sequence":"additional","affiliation":[{"name":"Islet Biology Group (IBEx), Exeter Centre of Excellence for Diabetes Research (EXCEED), University of Exeter College of Medicine and Health 5 , ,","place":["Exeter, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2893-3211","authenticated-orcid":false,"given":"James A M","family":"Shaw","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University 1 , 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