{"doi":"10.1530/joe-24-0190","title":"Identification of a vimentin-expressing α-cell phenotype in CF and normal pancreas","abstract":"Endocrine dysfunction and diabetes can develop secondary to fibrotic diseases within the pancreas, including cystic fibrosis (CF). 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 α-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 α-cells was seen in non-CF donors <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 α-cells. Differentiated α-cell function-associated gene expression was maintained. Differentially upregulated processes in co-expressing cells included pathways associated with extracellular matrix organisation, cell-cell adhesion, migratory capability and self-renewal. We have identified and characterised an intermediate epithelial/mesenchymal state in a sub-population of α-cells present throughout post-natal life, which may play a role in their response to extrinsic stressors, including fibrosis and ageing.","journal":"Journal of Endocrinology","year":2025,"id":550038,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":74020,"name":"Yan Hang","orcid":"0000-0002-5166-2480","position":1,"is_corresponding":false},{"id":690430,"name":"Nicole A. J. Krentz","orcid":"0000-0003-3622-2652","position":2,"is_corresponding":false},{"id":1445399,"name":"Lydia Russell","orcid":null,"position":3,"is_corresponding":false},{"id":1121385,"name":"Matthew R. Palmer","orcid":"0000-0002-3279-6563","position":4,"is_corresponding":false},{"id":506256,"name":"Christine S. Flaxman","orcid":"0009-0002-1144-7767","position":5,"is_corresponding":false},{"id":1445400,"name":"Nadine Plett","orcid":null,"position":6,"is_corresponding":false},{"id":1445401,"name":"Rowan Coulthard","orcid":null,"position":7,"is_corresponding":false},{"id":1445402,"name":"Yara Al-Selwi","orcid":null,"position":8,"is_corresponding":false},{"id":1444656,"name":"Nicola Dyson","orcid":"0000-0002-4173-1913","position":9,"is_corresponding":false},{"id":1444657,"name":"Minna Honkanen‐Scott","orcid":"0000-0002-6761-2998","position":10,"is_corresponding":false},{"id":44518,"name":"Seung K. Kim","orcid":"0000-0001-6135-7810","position":11,"is_corresponding":false},{"id":844521,"name":"Dina Tiniakos","orcid":"0000-0003-4657-7780","position":12,"is_corresponding":false},{"id":1376934,"name":"Günter Klöppel","orcid":"0000-0002-6688-086X","position":13,"is_corresponding":false},{"id":262817,"name":"Sarah J. Richardson","orcid":"0000-0002-1160-6062","position":14,"is_corresponding":false},{"id":690431,"name":"James Shaw","orcid":"0000-0002-2893-3211","position":15,"is_corresponding":false},{"id":1444655,"name":"Nicole Kattner","orcid":"0000-0002-2930-5719","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:54:12.321988Z","pmid":"39836539","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}