The helix-loop-helix protein ID2 governs NK cell fate by tuning their sensitivity to interleukin-15
Transcriptomics Dataset
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General Information
AccessionGSE76466
TitleThe helix-loop-helix protein ID2 governs NK cell fate by tuning their sensitivity to interleukin-15
DescriptionThe inhibitor of DNA binding 2 (Id2) is essential for NK cell development with its canonical role in this pathway being to antagonize E-proteins, silencing E-box gene expression and subsequent commitment to the T and B cell lineages. However, how E-box genes prevent NK cell development and homeostasis remains enigmatic. Here we identify a key role for Id2 in regulating the threshold for IL-15 receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Deletion of Id2 in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling. Id2-null NK cells displayed impaired IL-15 mediated JAK1/STAT5 phosphorylation, compromised metabolic function and enhanced apoptosis. Remarkably, Id2-null NK cell homeostasis could be fully rescued in vivo by IL-15 receptor stimulation and partially rescued by genetic ablation of Socs3. During normal NK cell maturation we observed an inverse correlation between the expression levels of E-protein target genes and Id2. These results shift the current paradigm on the role of Id2, indicating that it is not only required to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76466
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE76466
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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