Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 hours (h) after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.
The innate immune response to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice.
Sex, Specimen part
View SamplesMen are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that immune responses in the heart are phenotypically distinct in male compared to female mice 10 days after infection resulting in severe DCM in males.
Testosterone and interleukin-1β increase cardiac remodeling during coxsackievirus B3 myocarditis via serpin A 3n.
Sex, Specimen part, Treatment, Time
View SamplesWith the aim of understanding how Treg cells in highly vascularized tissues are related to Treg cells in other organs, we performed RNA-seq analysis of bulk Treg and Tconv cells isolated from liver, blood, spleen, and the liver-draining portal lymph node. This revealed a clear separation of cell transcriptomes by both tissue and Treg/Tconv identity, with cells from the liver falling between blood- and spleen-derived cells. Compared to splenic Treg cells, hepatic Treg cells were enriched for genes related to proliferation and activation, and genes encoding chemokine and cytokine receptors. Overall design: RNA was extracted from FACS-purified Tconv and Treg cells from various tissues of Foxp3Thy1.1 mice. Each sample contains cells pooled from 3 mice. 2 cell types from each of 4 tissues x 3 replicates = 24 samples.
CD49b defines functionally mature Treg cells that survey skin and vascular tissues.
Sex, Age, Specimen part, Cell line, Subject
View SamplesWhile unique subsets of Treg cells have been described in some non-lymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. We have identified a recirculating and highly suppressive effector Treg cell subset that expresses the a2 integrin, CD49b, and exhibits a unique tissue distribution. To identify genes and pathways enriched in CD49b+ Treg cells, we performed RNA-seq of splenic CD49b+ and CD49b- Treg cells that were of otherwise similar activation status based on expression of CD44 and CD62L. This revealed that splenic CD49b+ Treg cells express genes related to migration and activation, but are relatively depleted of genes whose expression is TCR-dependent in Treg cells. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculates through and surveys peripheral tissues. Overall design: RNA was extracted from FACS-purified splenic Tconv and Treg cells of different activation states from Foxp3GFP mice. 2 CD4+ T-cell lineages x 3 activation states x 4 replicates. There is no sample 3 (RNA was degraded); there are 23 samples in total.
CD49b defines functionally mature Treg cells that survey skin and vascular tissues.
Sex, Age, Specimen part, Cell line, Subject
View SamplesWhile unique subsets of Treg cells have been described in some non-lymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. We have identified a short-lived effector Treg cell subset that expresses the a2 integrin, CD49b, and exhibits a unique tissue distribution. Projection of the CD49b+ Treg signature onto the Treg phenotypic landscape as inferred by single-cell RNA-seq analysis, placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues. Overall design: Single-cell RNA-seq libraries (10x Genomics) were prepared from FACS-purified Tconv and Treg cells from pooled spleens of Foxp3GFP mice.
CD49b defines functionally mature Treg cells that survey skin and vascular tissues.
Sex, Age, Specimen part, Subject
View SamplesWe demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification.
Specimen part
View SamplesBackground: Moderate hypothermia (32oC for 12 72 hours) has therapeutic applications, but the mechanisms by which it affects cellular function are unclear. We tested the hypothesis that moderate hypothermia produces broad changes in gene expression by human cells at the level of mRNA.
Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA microarray study.
No sample metadata fields
View SamplesLong-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf +/+ and Plzf lu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing, conditional ablation, and busulfan challenge show that these are long-term SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index than EOMES- GFRA1+ spermatogonia in wild-type but not in Plzf lu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support a hierarchical model of a slow-cycling long-term SSC population supporting more rapid-cycling short-term SSCs. Overall design: 384-well plate-based 3'-end scRNA-seq was performed on two groups, Plzf +/+ and Plzf lu/lu, of cells across 4 plates. Plzf +/+ cells were spread across 2 plates and Plzf lu/lu cells were spread over 1 plate. The 4th plate contains both Plzf lu/lu (up to well C15) and Plzf +/+ (well C15 onward). Each sample in this record represents one plate.
Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF.
Specimen part, Cell line, Subject
View SamplesBackground: Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. Results: We estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%). Conclusion: We apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection. Overall design: Placental mRNA was sequenced on an Illumina GAIIx. Samples were derived from 4 human groups, 10 individuals per group, 2 samples per individual
Evaluating intra- and inter-individual variation in the human placental transcriptome.
No sample metadata fields
View SamplesThe glycopeptide antibiotic vancomycin (VCM) represents one of the last lines of defense against methicillin-resistant Staphylococcus aureus infections. However, vancomycin is nephrotoxic, but the mechanism of toxicity is still unclear.
Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.
Specimen part
View Samples