Single-cell transcriptome reveals the novel role of T-bet in suppressing the immature NK gene signature.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32406817.
- Also identified by DOI 10.7554/eLife.51339 and PMC identifier 7255804.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The transcriptional activation and repression during NK cell ontology are poorly understood. Here, using single-cell RNA-sequencing, we reveal a novel role for T-bet in suppressing the immature gene signature during murine NK cell development. Based on transcriptome, we identified five distinct NK cell clusters and define their relative developmental maturity in the bone marrow. 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. Since mTORC2 regulates the expression of T-bet through Akt<sup>S473</sup>-FoxO1 axis, we further characterized the T-bet-deficient NK cells and found an augmented immature transcriptomic signature. Moreover, deletion of <i>Foxo1</i> restores the expression of T-bet and corrects the abnormal expression of immature NK genes. Collectively, our study reveals a novel role for mTORC2-Akt<sup>S473</sup>-FoxO1-T-bet axis in suppressing the transcriptional signature of immature NK cells.
Medical subject headings
- Bone Marrow Cells
- Gene Expression Profiling
- Killer Cells, Natural
- Machine Learning
- RNA-Seq
- Single-Cell Analysis
- T-Box Domain Proteins
- Transcriptome