{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hu R"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)","Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)"],"pagination":["322-334"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10923889"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(3)"],"pubmed_abstract":["Pancreatic β-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of β cell specific Wfs1 knockout were applied to model β-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS β-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted β-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to β-cell failure. Notably, further investigation of t"],"journal":["Cell death and differentiation"],"pubmed_title":["ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models."],"pmcid":["PMC10923889"],"funding_grant_id":["31970751","81971078","32122030","32370855","82171166","21ZR1452400","32170740"],"pubmed_authors":["Xu M","Shao L","Le R","Li W","Su Q","Dai P","Gao Y","Gong M","Chen X","Wang X","Hu R","Wang Z","Zhang ZN"],"additional_accession":[]},"is_claimable":false,"name":"ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models.","description":"Pancreatic β-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of β cell specific Wfs1 knockout were applied to model β-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS β-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted β-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to β-cell failure. Notably, further investigation of t","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-07-15T11:57:42.108Z","creation":"2026-07-04T03:12:03.781Z"},"accession":"S-EPMC10923889","cross_references":{"pubmed":["38321214"],"doi":["10.1038/s41418-024-01258-w"]}}