{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Klein F"],"funding":["Swiss National Science Foundation","People Program"],"pagination":["638-655"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6400535"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["216(3)"],"pubmed_abstract":["T cell development is critically dependent on successful rearrangement of antigen-receptor chains. At the β-selection checkpoint, only cells with a functional rearrangement continue in development. However, how nonselected T cells proceed in their dead-end fate is not clear. We identified low CD27 expression to mark pre-T cells that have failed to rearrange their β-chain. Expression profiling and single-cell transcriptome clustering identified a developmental trajectory through β-selection and revealed specific expression of the transcription factor Duxbl at a stage of high recombination activity before β-selection. Conditional transgenic expression of Duxbl resulted in a developmental block at the DN3-to-DN4 transition due to reduced proliferation and enhanced apoptosis, whereas RNA silencing of Duxbl led to a decrease in apoptosis. Transcriptome analysis linked Duxbl to elevated expression of the apoptosis-inducing Oas/RNaseL pathway. RNaseL deficiency or sustained Bcl2 expression led to a partial rescue of cells in Duxbl transgenic mice. These findings identify Duxbl as a regulator of β-selection by inducing apoptosis in cells with a nonfunctional rearrangement."],"journal":["The Journal of experimental medicine"],"pubmed_title":["The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection."],"pmcid":["PMC6400535"],"funding_grant_id":["315902","310030B_160330/1","160330"],"pubmed_authors":["Klein F","von Muenchow L","Pelczar P","Rolink A","Engdahl C","Alberti-Servera L","Mitrovic M","Fehling HJ","Roux J","Tsapogas P"],"additional_accession":[]},"is_claimable":false,"name":"The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.","description":"T cell development is critically dependent on successful rearrangement of antigen-receptor chains. At the β-selection checkpoint, only cells with a functional rearrangement continue in development. However, how nonselected T cells proceed in their dead-end fate is not clear. We identified low CD27 expression to mark pre-T cells that have failed to rearrange their β-chain. Expression profiling and single-cell transcriptome clustering identified a developmental trajectory through β-selection and revealed specific expression of the transcription factor Duxbl at a stage of high recombination activity before β-selection. Conditional transgenic expression of Duxbl resulted in a developmental block at the DN3-to-DN4 transition due to reduced proliferation and enhanced apoptosis, whereas RNA silencing of Duxbl led to a decrease in apoptosis. Transcriptome analysis linked Duxbl to elevated expression of the apoptosis-inducing Oas/RNaseL pathway. RNaseL deficiency or sustained Bcl2 expression led to a partial rescue of cells in Duxbl transgenic mice. These findings identify Duxbl as a regulator of β-selection by inducing apoptosis in cells with a nonfunctional rearrangement.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2026-05-05T06:31:16.063Z","creation":"2025-05-29T20:02:47.556Z"},"accession":"S-EPMC6400535","cross_references":{"pubmed":["30765463"],"doi":["10.1084/jem.20181444"]}}