biostudies-literatureUnknownBlumhagen RZNHLBI NIH HHSWe used spatial transcriptomics from idiopathic pulmonary fibrosis (IPF) and unaffected control lung tissue to further understand the pathogenesis of MUC5B-driven lung fibrosis. We captured 43 fields of view in 15 IPF and 13 controls with and without the MUC5B promoter variant using the CosMx® platform and identified 19 cell types via semi-supervised clustering. MUC5B was ectopically expressed in AT2 cells in controls with the risk variant. We observed a decreased proportion of AT2 cells in controls and an increased proportion of aberrant basaloid cells in IPF associated with the MUC5B risk variant. We identified co-localized expression of MUC5B in respiratory bronchioles with 13 genes including the endoplasmic reticulum (ER) stress marker XBP1American journal of respiratory cell and molecular biologyhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12834077biostudies-literatureEctopic Expression of MUC5B in the Respiratory Bronchiole Initiates Endoplasmic Reticulum Stress in the IPF Lung.PMC12834077R01 HL158668UH3 HL123442P01 HL092870R01 HL097163UG3 HL151865P01 HL162607Cool CDDavidson EJSchwartz DAYang IVFingerlin TEBlumhagen RZKurche JSDobrinskikh EMa XHuber JPHeinz DfalseEctopic Expression of MUC5B in the Respiratory Bronchiole Initiates Endoplasmic Reticulum Stress in the IPF Lung.We used spatial transcriptomics from idiopathic pulmonary fibrosis (IPF) and unaffected control lung tissue to further understand the pathogenesis of MUC5B-driven lung fibrosis. We captured 43 fields of view in 15 IPF and 13 controls with and without the MUC5B promoter variant using the CosMx® platform and identified 19 cell types via semi-supervised clustering. MUC5B was ectopically expressed in AT2 cells in controls with the risk variant. We observed a decreased proportion of AT2 cells in controls and an increased proportion of aberrant basaloid cells in IPF associated with the MUC5B risk variant. We identified co-localized expression of MUC5B in respiratory bronchioles with 13 genes including the endoplasmic reticulum (ER) stress marker XBP12025-01-01T00:00:00Z2025 Oct2026-06-13T05:26:44.643Z2026-06-13T03:08:50.527ZS-EPMC128340774109108110.1165/rcmb.2025-0261OC10.1165/rcmb.2025-0261oc