Gene expression profiling has been performed on astrocytes isolated using laser capture microdissection (LCM) from multiple sclerosis normal appearing white matter (NAWM) and control WM to identify whether specific glial changes exist in NAWM which contribute to lesion development or prevent disease progression
Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role.
Specimen part, Disease
View SamplesmiR-155 has recently emerged as an important promoter of antitumor immunity through its functions in T lymphocytes. However, the impact of T cell expressed miR-155 on immune cell dynamics in solid tumors remains unclear. In the present study, we used single-cell RNA-sequencing to define the CD45+ immune cell populations within B16F10 murine melanoma tumors growing in either wild-type (WT) or miR-155 T cell conditional knockout (TCKO) mice at different timepoints. miR-155 was required for optimal T cell activation and reinforced the T cell response at the expense of infiltrating myeloid cells. Further, myeloid cells from tumors growing in TCKO mice were defined by an increase in wound healing genes and a decreased IFNg response gene signature. Finally, we found that miR-155 expression predicted a favorable outcome in human melanoma patients and was associated with a strong immune signature. Moreover, gene expression and histological analysis of the Cancer Genome Atlas (TCGA) data revealed that miR-155 expression also correlates with an immune-enriched subtype in 29 other human solid tumor types. Together, our study provides an unprecedented analysis of the cell types and gene expression signatures by immune cells within experimental melanoma tumors and elucidates miR-155's role in coordinating this dynamic response. Overall design: B16F10 murine melanoma cells expressing ovalbumin model antigen were injected subcutaneously (1e6) into wild-type (C57BL/6) and miR-155 T cell conditional knockout mice (n>4). 9 or 12 days after injection, tumors were pooled in each group, and DAPI(-)CD45(+) live tumor infiltrating immune cells were sorted via flow cytometry. Sorted immune cells were processed for single-cell RNA-sequencing via 10x platform.
MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers.
Specimen part, Cell line, Subject, Time
View SamplesDifferential gene expression profile of CD4+ T cells from 10 months old Wt, miR-155-/-, miR-146a-/- and DKO mice spleens. Overall design: Wt, miR-155-/-, miR-146a-/- and DKO mice were aged 10 months, CD4+ T cells were sorted from mice spleens for analyses.
miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.
No sample metadata fields
View SamplesDifferential gene expression profile of Tfh and non-Tfh cells from both Wt and miR-155-/- mice spleens. Overall design: Wt and miR-155-/- mice were immunized with OVA. 8 days post immunization, CD4+CXCR+PD1+ Tfh cells and CD4+CXCR5-PD1- non Tfh cells were sorted from mice spleens for analyses.
miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.
No sample metadata fields
View SamplesTumor associated CD4+ and CD8+ T cells were sorted from B16f10 OVA expressing tumors in miR-155 flox, miR-155 flox CD4Cre+, and miR-155 flox CD4Cre+ mice treated with immune checkpoint blocking (ICB) antibodies by flow sorting on CD45+CD3+CD4+ cells and CD45+ CD3+CD8+ cells. RNA was collected from these cells to perform RNA sequencing of total RNA. Overall design: Each sample represents cells from 2 to 3 individual tumors grown on individual mice that were pooled together before sorting via flow cytometry
Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade.
Cell line, Subject
View SamplesThe miR-155-dependent differences in gene expression in the HSPC compartment of FLT3-ITD mice is unknown. In this experiment, we performed RNA sequencing on FLT3-ITD and FLT3-ITD miR-155-/- mouse LKS cells. Overall design: RNA sequencing was performed on RNA extracted from Lin-, cKit+, Sca1+ cells isolated via flow cytometry from FLT3-ITD and FLT3-ITD miR-155-/- mice. 3 samples were submitted for sequencing for each experimental group. Each sample contains RNA from 3 mice, in order to get enough RNA from this rare stem cell population.
miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response.
Specimen part, Subject
View SamplesWe identify regulatory mechanisms that influence inflammation and metabolism during metabolic disease development. In addition to the other data represented in our paper, we performed RNA-seq to demonstrate a role for miR-146a, an anti-inflammatory miRNA, in regulating both inflammation and cellular metabolism during obesity. Overall design: Each sample represents pooled cells from three mice of the same genotype and treatment group. Samples were pooled before FACS to ensure sufficient cell numbers for sorting and RNA collection. WT or miR-146a-/- mice were treated with either high fat diet or normal chow diet for 14 weeks starting from 6 weeks of age. Mice were sacrificed and live, singlet CD45+ CD11b+ F4/80+ cells were sorted from the stromal vascular fraction of adipose tissue using FACS Aria. RNA was collected from the sorted cells via Qiazol/RNeasy Kit (Qiagen) and library preparation used Illumina TruSeq Stranded RNA Kit with Ribo-Zero Gold. RNA-seq was performed using Illumina HiSeq 50 cycle single-read sequencing version 4. Sequence alignment was performed through the University of Utah Bioinformatics Core Facility.
Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.
Specimen part, Subject
View SamplesBackground: Epithelial-to-Mesenchymal Transition (EMT) is predicted to play a critical role in tumor progression and metastasis in Hepatocellular Carcinoma. Our goal was to elucidate a mechanism of tumor proliferation and metastasis using a novel murine model of EMT.
Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion.
Specimen part
View SamplesTristetraprolin (TTP) is an RNA-binding protein that post-transcriptionally suppresses gene expression by delivering mRNA cargo to processing bodies (P-bodies) where the mRNA is degraded. TTP functions as a tumor suppressor in a mouse model of B cell lymphoma, and in some human malignancies low TTP expression correlates with reduced survival. Here we report important prognostic and functional roles for TTP in human prostate cancer. First, gene expression analysis of prostate tumors revealed low TTP expression correlates with patients having high-risk Gleason scores and increased biochemical recurrence. Second, in prostate cancer cells with low levels of endogenous TTP, inducible TTP expression inhibits their growth and proliferation, as well as their clonogenic growth. Third, TTP functions as a tumor suppressor in prostate cancer, as forced TTP expression markedly impairs the tumorigenic potential of prostate cancer cells in a mouse xenograft model. Finally, pathway analysis of gene expression data suggested metabolism is altered by TTP expression in prostate tumor cells, and metabolic analyses revealed that such processes are impaired by TTP, including mitochondrial respiration. Collectively, these findings suggest that TTP is an important prognostic indicator for prostate cancer, and augmenting TTP function would effectively disable the metabolism and proliferation of aggressive prostate tumors. Overall design: PC-3 cells were infected with a pRetroX-Tet-On-Advanced retrovirus and selected for by G418 resistance. Then the G418-resistant cells were secondarily infected with either a pRetroX-Tight-pPGK-tdTomato or a pRetroX-Tight-TTP-pPGK-tdTomato retrovirus and selected for by the expression of tdTomato. G418-resistant, tdTomato-positive cells were used for experiments, in triplicate for each cell type. Cells were treated with 300 ng/ml doxycycline (Dox) for 4h prior to collection. Cells infected with pRetroX-Tight-pPGK-tdTomato were used as controls.
Tristetraprolin disables prostate cancer maintenance by impairing proliferation and metabolic function.
Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesPurified phage was used to prevent tumor growth in a mouse model of bacteria aggravated-colorectal cancer. Composite E. coli phage or vehicle control was added to the drinking water of specific pathogen free (SPF) APCmin mice and animals were colonized with E.coli NC101. APCmin mice displayed no overall difference in the number of tumors that formed within the small intestine, however colonization with E. coli NC101 accelerated the growth of tumors resulting in a significant increase in large tumor formation. Importantly, bacteriophage treatment of AIEC colonized APCmin animals significantly reduced E. coli colonization. Overall design: 4 week old APCmin heterozygous mice were given a cocktail of 3 E. coli phage in drinking water for 4 weeks, then challenged with E. coli NC101 via oral gavage biweekly for 2 weeks. Mice were then maintained on drinking water containing phage mixture for 2 months.
Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis.
Specimen part, Cell line, Treatment, Subject
View Samples