Single-cell transcriptome reveals the novel role of T-bet in suppressing the immature NK gene signature the immature NK gene signature

Using scRNAseq, we identified five distinct NK cell clusters and define their relative developmental maturity in the murine bone marrow of WT mice. Transcriptome-based machine-learning classifiers revealed that half of the mTORC2-deficient NK cells belongs to the least mature NK cluster. Mechanistically, loss of mTORC2 results in an increased expression of signature genes representing immature NK cells. We further characterized the T-bet-deficient NK cells and found an augmented immature transcriptomic signature. Moreover, deletion of Foxo1 restores the expression of T-bet and corrects the abnormal expression of immature NK genes in Rictor-deficient NK cells. Overall design: Single-cell RNA-sequencing analysis of NK cells from bone marrow of WT, Rictor cKO, Rptor cKO, and Tbet KO mice