Single-cell gene expression reveals the stage-specific roles of TCF1 in T cell development and T cell malignancy

T cell factor 1 (TCF1; encoded by Tcf7) plays a critical role in T cell development and functions as a tumor suppressor by repressing the expression of LEF1 in the thymus. Here we reported the stage-specific regulation of TCF1 in early T cell differentiation and T cell malignancy despite the broad understand on the functions of TCF1. To illustrate the stage-specific functions of Tcf7 in T cell development and tumorigenesis, we applied single-cell transcriptional analysis to identify the precise trajectory of gene expression changes between the surface receptor-defined stages of T cell development. To systematically investigate the gene expression pattern in WT and stage-specific deletion of Tcf7, we sequenced 768 single cells from four genotype mice (WT, Tcf7-/-, Tcf7fl/flVav-cre, Tcf7fl/flLck-cre). The cell type of WT is DN1 (96 single cell) and DN2-3 (96 single cell). The cell type of Tcf7-/- is DN1 (96 single cell) and DN2-3 (96 single cell). The cell type of Tcf7fl/flVav-cre is DN1 (96 single cell) and DN2-3 (96 single cell). The cell type of Tcf7fl/flLck-cre is DN2-3 (192 single cell).