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Deconvoluting global cytokine signaling networks in natural killer cells [ChIP-Seq]

UID: 10806

Author(s): Lau, Colleen M.*, Sun, Joseph C.* * MSK affiliated

Description
Summary from the GEO: "Cytokine signaling via signal transducer and activator of transcription (STAT) proteins is crucial for optimal antiviral responses of natural killer (NK) cells. However, the pleiotropic effects of both cytokine and STAT signaling preclude the ability to precisely attribute molecular changes to either source. In this study, we employ a multi-“omics” approach to deconstruct and rebuild the complex interaction of three major STAT signaling pathways in NK cells. We uncover a global STAT4-STAT5 cooperative axis that is distinct and sometimes antagonistic to the STAT1 axis. We generate a network of STAT targets that highlights an integrated negative feedback loop, and demonstrate distinct STAT modes of epigenetic regulation. Finally, we identify shared signatures between mouse in vitro profiles and profiles from viral infection and humans, highlighting clinically translatable targets. Overall, we begin to unravel the intricate crosstalk between cytokine signaling pathways, and offer a valuable resource for improving cellular immunotherapy."

Overall design from the GEO: "ChIP-seq was performed on ex-vivo NK cells stimulated with various cytokine combinations."
Subject of Study
Mus musculus
Subject(s)
Cytokines
Epigenesis, Genetic
Killer Cells, Natural
Signal Transduction
STAT Transcription Factors
STAT4 Transcription Factor
STAT5 Transcription Factor
Access via GEO

BED and BIGWIG files of genome binding/occupancy profiling by high throughput sequencing
Accession #: GSE140043

Access via SRA

ChIP Sequencing data from 78 samples
Accession #: SRP228813

Access via BioProject

Additional information about the overall inititative.
Accession #: PRJNA588081

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files. The SRA Run Selector link at the bottom of the page is a processing tool for raw data.
Associated Publications
Wiedemann G, Grassmann S, Lau C, et al. Divergent role for STAT5 in the adaptive responses of natural killer cells. Cell Reports. 2020; 33(11):108498.
Wiedemann G, Santosa E, Grassmann S, et al. Deconvoluting global cytokine signaling networks in natural killer cells. Nature Immunology. 2021; 22(5):627-638.
Wiedemann G, Geary C, Lau C, et al. Cutting edge: STAT1-mediated epigenetic control of Rsad2 promotes clonal expansion of antiviral NK cells. Journal of Immunology. 2020; 205(1):21-25.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Illumina HiSeq 4000

High throughput gene sequencing system

Software Used
SRA Toolkit

The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.

Dataset Format(s)
SRA, BED, BIGWIG
Data Tool(s)
ChIP Seq
Dataset Size
12.8 Gb (TAR of BIGWIG), 868.5 KB (BED), 90 datasets ranging from 0.001 GB to 2.6 GB (SRA)
Data Catalog Record Updated
2023-12-07