We aim to identify genes differentially expressed between mouse WT and COUP-TFI_Nex-Cre mutant cortices.
Postmitotic control of sensory area specification during neocortical development.
Specimen part
View SamplesSolid cancers develop within a supportive microenvironment that promotes tumor formation and continued growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia) represent rich sources of these stromal factors. Leveraging a genetically-engineered mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumor (optic glioma), previous studies have demonstrated that microglia are important for glioma formation and maintenance. To identify the tumor-associated microglial factors that support glioma growth (gliomagens), we employed a comprehensive large scale discovery effort using optimized advanced RNA-sequencing methods. Candidate gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative RT-PCR and RNA FISH following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, Ccl5 was identified as a highly expressed chemokine in both genetically engineered Nf1 mouse and human optic gliomas. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, Ccl5 inhibition with neutralizing antibodies reduced Nf1 mouse optic glioma growth in vivo. Collectively, these findings establish Ccl5 as critical stromal growth factor in low-grade glioma maintenance relevant to future microglia-targeted therapies for brain tumors. Overall design: Nf1 optic glioma associated microglia from mice were flow sorted. Upregulated genes of glioma associated microglia were verified and further examined.
RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Sex, Age, Specimen part, Disease, Treatment
View SamplesAcute myeloid leukemia (AML), and other myeloid malignancies, are frequently treated with hypomethylating agents like decitabine. Alterations in the epigenome, induced by decitabine, are likely to result in gene expression changes. The effects of decitabine have not been systemically studied using primary AML samples.
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Specimen part, Disease, Treatment
View SamplesIn an attempt to elucidate the molecular mechanisms underlying the multiple roles of L1 in endothelium, we checked whether manipulating its expression affected the transcriptome of lECs. To this purpose, we compared the gene expression profiles of L1-overexpressing and control lECs by Affymetrix, which revealed a remarkable effect of L1 overexpression on lECs transcriptome.
Endothelial deficiency of L1 reduces tumor angiogenesis and promotes vessel normalization.
Specimen part
View SamplesThe goal of this gene expression profiling experiment was to identify the entire set of transcription factors expressed during late pupal wing development (~80h APF) when pigmentation genes are expressed
Emergence and diversification of fly pigmentation through evolution of a gene regulatory module.
Specimen part
View SamplesNeutrophils 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
Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy.
Specimen part
View SamplesSpinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease and is the second most common genetic disorder leading to death in childhood. Motoneurons derived from induced pluripotent stem cells (iPS cells) obtained by reprogramming SMA patient and his healthy father fibroblasts, and genetically corrected SMA-iPSC obtained converting SMN2 into SMN1 with target gene correction (TGC), were used to study gene expression and splicing events linked to pathogenetic mechanisms.
Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of key regions and genes important in the pathogenesis of sezary syndrome by combining genomic and expression microarrays.
Specimen part, Disease
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