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SRP090798
Mus musculus
25 Downloadable Samples
Illumina HiSeq 2000
Description
Recent efforts have uncovered immense transcriptional and ontogenetic diversity among tissue-resident macrophages, each with their own transcriptional profile endowing the cell with its tissue-specific functions. However, it is currently unknown whether the origins of different macrophage populations may affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone marrow-derived macrophages (BMDM) are even present in tumors of the brain, a tissue where there is no homeostatic involvement of peripherally-derived myeloid cells. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing models to demonstrate that BMDM are indeed abundant in primary and metastatic brain tumors. Transcriptional profiling of tumor-associated BMDM and resident microglia showed that these cells acquire substantially different gene expression profiles. Our data suggest that transcriptional networks in each cell population are associated with tumor-mediated education, yet are also influenced by chromatin landscapes established before tumor initiation. Furthermore, we demonstrate that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between brain-resident microglia and peripherally-derived macrophages in both primary and metastatic disease in mouse and human. Overall design: Tumor associated microglia and macrophages were isolated from mouse glioma tumors. Samples are provided as matched microglia and macrophages from 3 tumors.
Publication Title
Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor in adults, can be divided into several molecular subtypes including proneural GBM. Most clinical strategies aimed at directly targeting glioma cells in these tumors have failed. A promising alternative is to target stromal cells in the brain microenvironment, such as tumor-associated microglia and macrophages (TAMs). Macrophages are dependent upon colony stimulating factor (CSF)-1 for differentiation and survival; therefore, we used an inhibitor of its receptor, CSF-1R, to target macrophages in a mouse proneural GBM model. CSF-1R inhibition dramatically increased survival in mice and regressed established GBMs. Tumor cell apoptosis was significantly increased, and proliferation and tumor grade markedly decreased. Surprisingly, TAMs were not depleted in tumors treated with the CSF-1R inhibitor. Instead, analysis of gene expression in TAMs isolated from treated tumors revealed a decrease in alternatively activated/ M2 macrophage markers, consistent with impaired tumor-promoting functions. These gene signatures were also associated with better survival specifically in the proneural subtype of patient gliomas. Collectively, these results establish macrophages as valid therapeutic targets in proneural gliomas, and highlight the clinical potential for CSF-1R inhibitors in GBM.
Publication Title
CSF-1R inhibition alters macrophage polarization and blocks glioma progression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The aim of this study was to determine how gene expression is changed after arsenite-induced malignant transformation of prostate epithelial cells.
Publication Title
Coordinate H3K9 and DNA methylation silencing of ZNFs in toxicant-induced malignant transformation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell diseases characterized by dysplasia of one or more hematologic lineages and a high-risk of developing acute myeloid leukemia (AML). MDS patients have recurrent bacterial infections and abnormal expression of CD56 by monocytes. We investigated MDS patients’ bone marrow CD56+/CD56- monocytes and their in vitro derived dendritic cell (DCs) populations in comparison to cells obtained from disease-free subjects. We found that monocytes from MDS patients, irrespective of CD56 expression, have reduced phagocytosis activity and low expression of genes involved in triggering immune responses, regulation of immune and inflammatory response signaling pathways, and in the response to lipopolysaccharide. Dendritic cells (DCs) derived in vitro from MDS monocytes failed to develop dendritic projections and had reduced expression of HLA-DR and CD86 suggesting that antigen processing and T cell activation capabilities are impaired. In conclusion, we identified in both CD56+ and CD56- monocytes from MDS-patients several abnormalities that may be related to the increased susceptibility to infections observed in these patients.
Publication Title
Bone Marrow Monocytes and Derived Dendritic Cells from Myelodysplastic Patients Have Functional Abnormalities Associated with Defective Response to Bacterial Infection.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 88 Downloadable Samples
- Illumina HiSeq 2500
Description
FSHD and control immortalised myoblasts show repression of Pax7 target genes Overall design: FSHD Myoblasts 54-2, 54-12, 54-A5, 16A and 12A and matched controls 54-6, 54-A10, 16U and 12U were plated at 312,000 cells per 12 well plate in proliferation media and cultured for 48 hours or until 100% confluent. RNA-sequencing was performed on high quality (RIN > 8.0) DNA free RNA.
Publication Title
PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Comparing WT mice to a mouse model of mental retardation, this work identifies genes which display differences in ribosome-bound mRNAs, in hippocampus CA1 pyramidal cells. These genes products are potent functional components of neuronal plasticity and hippocampus-dependent memory. Overall design: Using a triple transgenic mouse line, we immunoprecipitated the HA-Rpl22 protein to isolate and sequence ribosome-associated mRNA in CA1 pyramidal cells. Pairwise comparison of wild type and Fmr1 KO mice defined a specific gene expression profile.
Publication Title
Cell Type-Specific mRNA Dysregulation in Hippocampal CA1 Pyramidal Neurons of the Fragile X Syndrome Mouse Model.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
The function of Structural maintenance of chromosome flexible domain containing 1 (Smchd1) was examined during mouse preimplantation development using an siRNA knockdown approach. Transient SMCHD1 deficiency during the period between fertilization and morula/early blastocyst stage compromised embryo viability and resulted in reduced cell number, reduced embryo diameter, and reduced nuclear volumes at the morula stage. RNAseq analysis of Smchd1 knockdown morulae revealed aberrant increases in expression of mRNAs related to the trophoblast lineage, indicating SMCHD1 inhibits trophoblast lineage gene expression and promotes inner cell mass formation. siRNA knockdown also reduced expression of cell proliferation genes, including S-phase kinase-associated protein 2 (Skp2). Smchd1 expression was elevated in Caudal type homeobox transcription factor 2 (Cdx2)-/- blastocysts, indicating enriched expression, and further indicating a role in inner cell mass development. These results indicate that Smchd1 plays dual roles in the preimplantation embryo, promoting a lineage-appropriate pattern of gene expression supporting inner cell mass formation, whilst controlling lineage formation and gene expression in the trophectoderm. Overall design: Effects of SMCHD1 siRNA knockdown were tested in mouse embryos
Publication Title
Novel key roles for structural maintenance of chromosome flexible domain containing 1 (Smchd1) during preimplantation mouse development.
Sample Metadata Fields
Treatment, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
In order to analyze the global changes in gene expression resulting from loss of Fra signaling, we performed a microarray experiment comparing Drosophila embryos containing a loss of function fra[3] mutation to age matched wildtype
Publication Title
Requirement for commissureless2 function during dipteran insect nerve cord development.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
In order to analyze the global changes in gene expression resulting from induction of NetA-Fra signaling, we carried out a microarray experiment comparing Drosophila third instar wing imaginal discs in which Net+Fra had been overexpressed to age matched wild type wing imaginal discs.
Publication Title
Requirement for commissureless2 function during dipteran insect nerve cord development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify novel PPARalpha target genes involved in lipid metabolism
Publication Title
Evolutionarily conserved gene family important for fat storage.
Sample Metadata Fields
No sample metadata fields
View Samples