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INKT cells RNA-Seq (WT vs SFR KO)

ABSTRACT: iNKT cells RNA-Seq (WT vs SFR KO)

PROVIDER: PRJNA486367 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7703384_1.fastq.gz	Fastqsanger.gz
	SRR7703384_2.fastq.gz	Fastqsanger.gz
	SRR7703385_1.fastq.gz	Fastqsanger.gz
	SRR7703385_2.fastq.gz	Fastqsanger.gz
	SRR7703386_1.fastq.gz	Fastqsanger.gz

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iNKT cells RNA-Seq (WT vs SFR KO)

Project description:RNA transcriptome difference between WT and SFR KO iNKT cells To understand how SLAM family receptors (SFRs) contribute to iNKT cell development, a mouse lacking all SFRs in addition to the ligand of 2B4, CD48, was generated, and the transcriptional profiles of thymic iNKT cells from wild-type and SFR KO mice were compared, using RNA sequencing.

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Project description:iNKT cells are a T lymphocyte subset displaying an innate effector phenotype that is acquired through a thymic developmental program controlled by microRNAs (miRNAs). iNKT cells lacking all miRNAs by the deletion of Dicer (Dicer KO) are markedly reduced and display a complete maturation block. In this study, we sought to gain insight into the miRNA-regulated genetic program required for iNKT cell development. By systemic analysis, we identified transcripts differentially expressed between thymic WT or Dicer KO iNKT cells and targeted by the iNKT cell-specific miRNAs. TGF-βRII, a molecule critically implicated in iNKT cell maturation, was found upregulated in Dicer KO iNKT cells together with increased TGF-β-dependent signaling. miRNAs belonging to the paralog miR-106a~363, miR-106b~25 and miR-17~92 clusters were predicted to target TGF-βRII mRNA during iNKT cell development. Thymic iNKT cells lacking all three miRNA clusters displayed both increased TGF-βRII expression and signaling and a maturation block, recapitulating those found in Dicer KO iNKT cells. Consistently, inhibition of TGF-β-dependent signaling in the absence of miRNAs, by crossing TGF-βRII KO and Dicer KO mice, rescued iNKT cell maturation. Collectively, our results highlight a fundamental requirement of the modulation of TGF-β-dependent signaling by miRNAs for iNKT cell development

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