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TCF1 dosage determines cell fate during T cell development. [scRNA-Seq]

GSE275718 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/10/18 Platform GPL24247
Summary
Loss of function studies have shown that transcription factor T cell factor-1 (TCF1), encoded by the Tcf7 gene, is essential for T cell development in the thymus. We discovered that the Tcf7 expression level is regulated by E box DNA binding proteins, independent of Notch, and regulates ab and gd T cell development. Systematic interrogation of the five E-protein binding elements (EPE1-5) in the Tcf7 enhancer region showed lineage-specific utilization. Specifically, loss-of-function analysis revealed that only EPE3 plays a critical role in supporting ab T cell development, while EPE1, 3 and 5 regulate gd T cell maturation and functional cell fate decision. The importance of EPE3 in supporting both lineages may stem from its unique capacity to interact with the Tcf7 transcriptional start site. Together these studies demonstrate that the precise dosage of TCF1 expression mediated by distinct EPEs generates a balanced output of T cells from the thymus.
Published in
TCF1 dosage determines cell fate during T cell development
Verma A, Aylward B, Ma F et al. · Science advances 2024 · PMID 39602533 · doi:10.1126/sciadv.ado5982
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Also filed as BioProject PRJNA1152614 and SRA study SRP528752. Searching any of these in the dataset finder brings you back here.

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