Single-cell transcriptome reveals the novel role of T-bet in suppressing the immature NK gene signature.
Chao YangJason R SiebertRobert BurnsYongwei ZhengAo MeiBenedetta BonacciDemin WangRaul A UrrutiaMatthew J RieseSridhar RaoKaren-Sue CarlsonMonica S ThakarSubramaniam MalarkannanPublished in: eLife (2020)
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 AktS473-FoxO1 axis, 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. Collectively, our study reveals a novel role for mTORC2-AktS473-FoxO1-T-bet axis in suppressing the transcriptional signature of immature NK cells.
Keyphrases
- nk cells
- single cell
- rna seq
- genome wide
- poor prognosis
- signaling pathway
- transcription factor
- high throughput
- machine learning
- bone marrow
- gene expression
- genome wide identification
- copy number
- binding protein
- dna methylation
- long non coding rna
- big data
- artificial intelligence
- cell proliferation
- wild type
- heat stress