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SRP173228
Mus musculus
16 Downloadable Samples
NextSeq 500
Description
Neutrophils represent a fundamental mechanism of antimicrobial resistance and inflammation 1. Moreover, neutrophils have emerged as important players in the activation, orchestration and regulation of adaptive immune responses2,3. Neutrophils are a component of the tumor microenvironment (TME) and have been prevalently shown to promote progression 4-6. On the other hand, unleashed neutrophilic effectors have also been reported to mediate anti-cancer resistance7-11. Antibody-mediated depletion used to investigate the role of neutrophils in tumor progression suffers from limitations, including duration, specificity and perturbation of the system12. We therefore used a genetic approach to investigate the role of neutrophils in primary 3-methylcholanthrene (3-MCA)-induced sarcomagenesis. Neutrophils were found to play an essential role in resistance against primary carcinogenesis by driving an interferon-? dependent type 1 immune response. Neutrophil-dependent macrophage production of IL-12p70 led to type 1 polarization of CD4- CD8- unconventional aß T cells (UTCaß) in the TME. Single cell RNAseq analysis and in vivo evidence from two preclinical sarcoma models highlight the antitumor potential of a UTCaß subset. In the TCGA cohort of human undifferentiated pleomorphic sarcomas (UPS), unlike other sarcomas, granulocyte-colony stimulating factor receptor (CSF3R) expression and a neutrophil signature were associated with better outcome and with a type 1 immune response. The positive association between high neutrophil infiltration and improved clinical outcome was confirmed in an independent UPS cohort by immunohistochemistry. Thus, neutrophils, by driving a type 1 immune response and polarization of UTCaß, mediate resistance against murine and human sarcomas. Overall design: two experimental conditions, two biological replicates for each condition
Publication Title
Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, in addition, the mechanisms underlying sublingual immunotherapy (SLIT) are still unknown.
Publication Title
Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation.
Publication Title
Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Muscle Expression of SOD1(G93A) Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 457 Downloadable Samples
- Illumina HiSeq 2000
Description
Transdifferentiation of fibroblasts into induced Neuronal cells (iNs) by neuronal-specific transcription factors Brn2, Myt1l and Ascl1 is a paradigmatic example of inter-lineage conversion across epigenetically distant cells. Despite tremendous progress on the transcriptional hierarchy underlying transdifferentiation, the enablers of the concomitant epigenome resetting remain to be elucidated. Here we investigated the role of KMT2A and KMT2B, two histone H3 lysine 4 methylases with cardinal roles in development, through individual and combined inactivation. We found that Kmt2b, whose human homologue's mutations cause dystonia, is selectively required for iN conversion through the suppression of the alternative myocyte program and the induction of neuronal maturation genes. Overall design: In order to study the role of KMT2A and KMT2B during transdifferentiation, we employed conditional mouse strains carrying: i) the exon 2 of Kmt2a and/or Kmt2b flanked by LoxP sites; ii) the knock-in of the YFP-coding gene into one Rosa26 allele, downstream of a LoxP-flanked transcription termination cassette (STOP cassette); and iii) the gene coding for the tamoxifen-inducible version of Cre recombinase knocked into the second Rosa26 allele (Glaser et al., 2006; Kranz et al., 2010; Testa et al., 2004). MEFs were derived from Kmt2a (and/or Kmt2b)fl/fl Cre+ YFP+ embryos and from Kmt2a+/+Kmt2b+/+ Cre+ YFP+ or Kmt2afl/+ Cre+ YFP+ for Kmt2a conditional KO (cKO) as controls (Figure 1A), and were subjected to transdifferentiation. After 13 days of BAM treatment, cells were FACS sorted for PSA-NCAM expression, and the transcriptome of positive and negative cells were independently profiled.
Publication Title
KMT2B Is Selectively Required for Neuronal Transdifferentiation, and Its Loss Exposes Dystonia Candidate Genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Inflammatory diseases such as Aicardi-Goutieres Syndrome (AGS) and severe systemic lupus erythematosus (SLE) are generally lethal disorders that have been traced to defects in the exonuclease Trex1 (DNAseIII). Mice lacking Trex1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the STING (stimulator of interferon genes) pathway. Here we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into Trex1-/- mice. Trex1-/- macrophages did not exhibit significant augmented ability to produce pro-inflammatory cytokines compared to normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. These results shed molecular insight into inflammation and provide concepts for the design of new therapies.
Publication Title
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Activation of the STING (Stimulator of Interferon Genes) pathway by microbial or self-DNA, as well as cyclic di nucleotides (CDN), results in the induction of numerous genes that suppress pathogen replication and facilitate adaptive immunity. However, sustained gene transcription is rigidly prevented to avoid lethal STING-dependent pro-inflammatory disease by mechanisms that remain unknown. We demonstrate here that after autophagy-dependent STING delivery of TBK1 (TANK-binding kinase 1) to endosomal/lysosomal compartments and activation of transcription factors IRF3 (interferon regulatory factors 3) and NF-B (nuclear factor kappa beta), that STING is subsequently phosphorylated by serine/threonine UNC-51-like kinase (ULK1/ATG1) and IRF3 function is suppressed. ULK1 activation occurred following disassociation from its repressor adenine monophosphate activated protein kinase (AMPK), and was elicited by CDNS generated by the cGAMP synthase, cGAS. Thus, while CDNs may initially facilitate STING function, they subsequently trigger negative-feedback control of STING activity, thus preventing the persistent transcription of innate immune genes.
Publication Title
Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Inflammatory diseases such as Aicardi-Goutieres Syndrome (AGS) and severe systemic lupus erythematosus (SLE) are generally lethal disorders that have been traced to defects in the exonuclease Trex1 (DNAseIII). Mice lacking Trex1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the STING (stimulator of interferon genes) pathway. Here we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into Trex1-/- mice. Trex1-/- macrophages did not exhibit significant augmented ability to produce pro-inflammatory cytokines compared to normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. These results shed molecular insight into inflammation and provide concepts for the design of new therapies.
Publication Title
Intrinsic self-DNA triggers inflammatory disease dependent on STING.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We analyzed transcriptional changes in 4 prostate cancer cell lines following treatment with the BET inhibitor I-BET762 using Affymetrix Human Genome U133 Plus 2.0 Arrays.
Publication Title
Inhibition of BET bromodomain proteins as a therapeutic approach in prostate cancer.
Sample Metadata Fields
Cell line, Time
View Samples