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Runx, Tcf/Lef, and Tle factors underpin the inception of T cell fate

GSE264410 Mus musculus Expression profiling by high throughput sequencing; Other; Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/09/17 Platform GPL34290
Summary
The goal of this study is to resolve the heterogeneity of transcriptomic and chromatin accessibility (ChrAcc) landscape in DN1 thymocytes harboring ETPs. Comparison of molecular features between ETPs with non-ETP DN1 cells predicted contribution by Runx and Tcf/Lef family transcription factors, and pre-thymic ablation of Runx1/3, Tcf1/Lef1, or their common Tle/Groucho cofactors invariably impaired ETP formation. Single cell analysis of the factor-targeted ETPs revealed that these three sets of factors converged on Notch1 or Notch pathway effector molecules including Hes1 and Hhex, to support their transcriptional activation by acting on shared and distinct regulatory elements. Furthermore, Runx and Tcf/Lef deficiency caused thymic expansion of myeloid and B cells, respectively, while loss of Tle/Groucho factors resulted in broader diversion to multiple non-T lineages
Published in
Single-cell multiomics identifies Tcf1 and Lef1 as key initiators of early thymic progenitor fate
Zhao X, Hu SS, Lee WH et al. · Science immunology 2025 · PMID 40938954 · doi:10.1126/sciimmunol.adq8970
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Also filed as BioProject PRJNA1102365 and SRA study SRP502864. Searching any of these in the dataset finder brings you back here.

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