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SRP159400
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
Using complementary forms of high dimensional profiling we define differences in CD45+ cells from syngeneic mouse tumors that either grow progressively or eventually reject following immune checkpoint therapy (ICT). Unbiased assessment of gene expression of tumor infiltrating cells by single cell RNA sequencing (scRNAseq) and longitudinal assessment of cellular protein expression by mass cytometry (CyTOF) revealed significant remodeling of both the lymphoid and myeloid intratumoral compartments. Surprisingly, we observed multiple subpopulations of monocytes/macrophages distinguishable by the combinatorial presence or absence of CD206, CX3CR1, CD1d and iNOS, markers of different macrophage activation states that change over time during ICT in a manner partially dependent on IFN?. Both the CyTOF data and additional analysis of scRNAseq data support the hypothesis that macrophage polarization/activation results from effects on circulatory monocytes/early macrophages entering tumors rather than on pre-polarized mature intratumoral macrophages. Thus, ICT induces transcriptional and functional remodeling of both myeloid and lymphoid compartments. Overall design: Droplet-based 3' end massively parallel single-cell RNA sequencing was performed by encapsulating sorted live CD45+ tumor infiltrating cells into droplets and libraries were prepared using Chromium Single Cell 3' Reagent Kits v1 according to manufacturer's protocol (10x Genomics). The generated scRNAseq libraries were sequenced using an Illumina HiSeq2500.
Publication Title
High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The lack of mouse models permitting the specific ablation of tissue-resident macrophages and monocyte-derived cells complicates understanding of their contribution to tissue integrity and to immune responses. Here we use a new model permitting diphtheria-toxin (DT)-mediated depletion of those cells and in which dendritic cells are spared. We showed that the myeloid cells of the mouse ear skin dermis are dominated by a population of melanin-laden macrophages, called melanophages, that has been missed in most previous studies. By using gene expression profiling, DT-mediated ablation and parabiosis, we determined their identity including their similarity to other skin macrophages, their origin and their dynamics. Limited information exist on the identity of the skin cells responsible for long-term tattoo persistence. Benefiting of our knowledge on melanophages, we showed that they are responsible for retaining tattoo pigment particles through a dynamic process which characterization has direct implications for improving strategies aiming at removing tattoos.
Publication Title
Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 29 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A macrophage gene expression signature defines a field effect in the lung tumor microenvironment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
AJ mouse is susceptible to lung carcinogenesis from urethane treatment and is a good model for human adenocarcinoma. We completed a study using microarray analysis of bronchoalveolar lavage cells from control or urethane treated mice. A unique macrophage expression signature in the lung tumor microenvironment was able to correctly classify the lavage samples.
Publication Title
A macrophage gene expression signature defines a field effect in the lung tumor microenvironment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The aim of the dataset was to study on a genome-wide level the impact of Lat deficiency on gene expression in resting and activated CD4+ T cells
Publication Title
Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- NextSeq 500
Description
Here, using genome wide analysis, we demonstrate that canonical mRNA is processed post-transcriptionally through an alternative cleavage and polyadenylation mechanism. As a result of this process, the downstream cleavage fragment of the 3'UTR remains uncapped and stable This finding indicates that different parts of gene mRNA are separate and independent, by re-annotating the human transcriptome using this model, we provide a new overview of the function and impact of microRNA (miRNA) Our results shed new light on the mammalian transcriptome and show that what were considered as 3'UTRs are in fact autonomous RNA fragments. Overall design: Examination of mRNA levels and cleavage across transcripts in U2OS and 293 cell types (3 replicates each)
Publication Title
Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 308 Downloadable Samples
- Illumina HiSeq 2500
Description
One of sleep's putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience, however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine, and behavioral variables, as well as the brain and blood transcriptome in mice exposed to 9 weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypical variables revealed that rapid-eye-movement sleep (REMS), corticosterone regulation, and coat state were most responsive to UCMS. REMS theta oscillations were enhanced, whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus, and blood were associated with inflammatory and immune responses. A machine-learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters that were enriched in 193 pathways, including some involved in stem cells, immune response, apoptosis, and survival. Only three pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS, and anhedonia shared pathways involved in oxidative stress, cell proliferation, and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences. Overall design: Study of transcriptomic changes in three stress- and sleep-related brain regions (prefrontal cortex, hippocampus, hypothalamus) and blood following 9 weeks of Unpredictable Chronic Mild Stress (UCMS) in mice.
Publication Title
REM sleep's unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Psoriasis is a chronic inflammatory skin disease of unknown etiology. Although macrophages and dendritic cells (DCs) have been proposed to drive the psoriatic cascade, their largely overlapping phenotype hampered studying their respective role. Topical application of Imiquimod, a Toll-like receptor 7 agonist, induces psoriasis in patients and psoriasiform inflammation in mice. We showed that daily application of Imiquimod for 14 days recapitulated both the initiation and the maintenance phase of psoriasis. Based on our ability to discriminate Langerhans cells (LCs), conventional DCs, monocytes, monocyte-derived DCs and macrophages in the skin, we characterized their dynamics during both phases of psoriasis. During the initiation phase, neutrophils infiltrated the epidermis whereas monocytes and monocyte-derived DCs were predominant in the dermis. During the maintenance phase, LCs and macrophage numbers increased in the epidermis and dermis, respectively. LC expansion resulted from local proliferation, a conclusion supported by transcriptional analysis. Continuous depletion of LCs during the course of Imiquimod treatment aggravated chronic psoriatic symptoms as documented by an increased influx of neutrophils and a stronger inflammation. Therefore, by developing a mouse model that mimics the human disease more accurately, we established that LCs play a negative regulatory role during the maintenance phase of psoriasis.
Publication Title
Dynamics and Transcriptomics of Skin Dendritic Cells and Macrophages in an Imiquimod-Induced, Biphasic Mouse Model of Psoriasis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens.
Publication Title
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 57 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Choroid plexus carcinomas (CPC) are poorly understood and frequently lethal brain tumors with minimal treatment options. Using a new mouse model of the disease and a large cohort of human CPCs [GSE60892; GSE60899], we performed a cross-species, genome-wide search for novel oncogenes within syntenic regions of chromosome gain. TAF12, NFYC and RAD54L, co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3, were identified as oncogenes that are gained in tumors in both species and required to initiate and progress the disease in mice. TAF12 and NFYC are transcription factors that regulate the epigenome, while RAD54L plays a central role in DNA repair. Our data identify a group of concurrently gained, novel oncogenes that cooperate in the formation of CPC and unmask potential new avenues for therapy.
Publication Title
Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes.
Sample Metadata Fields
No sample metadata fields
View Samples