{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Katzen J"],"funding":["BLRD VA","NHLBI NIH HHS"],"pagination":["e2123187119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9618079"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(43)"],"pubmed_abstract":["Disruption of alveolar type 2 cell (AEC2) protein quality control has been implicated in chronic lung diseases, including pulmonary fibrosis (PF). We previously reported the in vivo modeling of a clinical surfactant protein C (SP-C) mutation that led to AEC2 endoplasmic reticulum (ER) stress and spontaneous lung fibrosis, providing proof of concept for disruption to proteostasis as a proximal driver of PF. Using two clinical SP-C mutation models, we have now discovered that AEC2s experiencing significant ER stress lose quintessential AEC2 features and develop a reprogrammed cell state that heretofore has been seen only as a response to lung injury. Using single-cell RNA sequencing in vivo and organoid-based modeling, we show that this state arises de novo from intrinsic AEC2 dysfunction. T"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Disruption of proteostasis causes IRE1 mediated reprogramming of alveolar epithelial cells."],"pmcid":["PMC9618079"],"funding_grant_id":["K08 HL150226","I01 BX005411","R01 HL087825","I01 BX001176","U01 HL134745","U01 HL152970","R01 HL132999","R01 HL152194","K08 HL163398","R01 HL145408"],"pubmed_authors":["Rodriguez L","Beers MF","Katzen J","Carl J","Morley M","Pelura T","Rosen G","Leach JP","Mulugeta S","Zhao M","Carson P","Murthy A","Morrisey EE","Babu A","Barrett M","McGraw MD","Tomer Y","Basil MC"],"additional_accession":[]},"is_claimable":false,"name":"Disruption of proteostasis causes IRE1 mediated reprogramming of alveolar epithelial cells.","description":"Disruption of alveolar type 2 cell (AEC2) protein quality control has been implicated in chronic lung diseases, including pulmonary fibrosis (PF). We previously reported the in vivo modeling of a clinical surfactant protein C (SP-C) mutation that led to AEC2 endoplasmic reticulum (ER) stress and spontaneous lung fibrosis, providing proof of concept for disruption to proteostasis as a proximal driver of PF. Using two clinical SP-C mutation models, we have now discovered that AEC2s experiencing significant ER stress lose quintessential AEC2 features and develop a reprogrammed cell state that heretofore has been seen only as a response to lung injury. Using single-cell RNA sequencing in vivo and organoid-based modeling, we show that this state arises de novo from intrinsic AEC2 dysfunction. T","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2025-04-04T07:11:09.724Z","creation":"2025-04-04T07:11:09.724Z"},"accession":"S-EPMC9618079","cross_references":{"pubmed":["36252035"],"doi":["10.1073/pnas.2123187119"]}}