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

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

PROVIDER: PRJNA631285 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11741810.fastq.gz	Fastqsanger.gz
	SRR11741811.fastq.gz	Fastqsanger.gz
	SRR11741812.fastq.gz	Fastqsanger.gz
	SRR11741813.fastq.gz	Fastqsanger.gz
	SRR11741814.fastq.gz	Fastqsanger.gz

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

Project description: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.

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

Project description: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.

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