{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin B"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS","NCI NIH HHS"],"pagination":["869-877"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11890216"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["629(8013)"],"pubmed_abstract":["Airway hillocks are stratified epithelial structures of unknown function<sup>1</sup>. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia<sup>2,3</sup>. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer."],"journal":["Nature"],"pubmed_title":["Airway hillocks are injury-resistant reservoirs of unique plastic stem cells."],"pmcid":["PMC11890216"],"funding_grant_id":["UG3 CA268117","F31 HL165736","UH3 CA268117","P30 DK135043","R01 HL157221","P30 DK057521","R01 HL118185","T32 HL116275","U24 HL148865","P30 DK043351","K08 HL124298","R01 HL142559"],"pubmed_authors":["Vinarsky V","Waghray A","Shah VS","Hariri LP","Villoria J","Shipkovenska GG","Hintschich CA","Capen DE","Xu J","Lin B","Chernoff C","Dou Z","Rajagopal J","Surve MV","Leduc AD","Sun J","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"Airway hillocks are injury-resistant reservoirs of unique plastic stem cells.","description":"Airway hillocks are stratified epithelial structures of unknown function<sup>1</sup>. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia<sup>2,3</sup>. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T18:01:37.554Z","creation":"2025-04-04T02:54:34.069Z"},"accession":"S-EPMC11890216","cross_references":{"pubmed":["38693267"],"doi":["10.1038/s41586-024-07377-1"]}}