Single-cell multiomics identifies Tcf1 and Lef1 as key initiators of early thymic progenitor fate.

ABSTRACT: Bone marrow-derived multipotent hematopoietic progenitors seed the thymus and generate early thymic progenitors (ETPs). However, the factors governing ETP formation remain poorly defined. Using single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq), we dissected the heterogeneity of transcriptomic and chromatin accessibility landscapes in murine ETPs. Whereas Tcf1^- ETPs exhibited higher proliferative capacity, Tcf1⁺ ETPs appeared to be immediate, more robust precursors to T lineage-specified early thymocytes. Prethymic ablation of Tcf1 and its homolog Lef1 severely impaired ETP formation in vivo. Whereas ablating Tcf1 alone had limited impact, loss of both Tcf1 and Lef1 impaired transcriptional ac

SUBMITTER: Zhao X 

PROVIDER: S-EPMC12700322 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature