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GSE102453
Mus musculus
13 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Preconditioning with a small dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response to preconditioning remains unknown. Using the kidney as a model organ, we identify the essential role of the renal epithelial cell in mediating the full expression of protective preconditioning. The protective phenotype is characterized by the clustering of macrophages around S1 segments of proximal tubules, which forms a functional unit mediating protection. To investigate the molecular pathways, we laser microdissected S1 segments from the following: 1) Non-preconditioned mice subjected to single-dose 5 mg/kg lipopolysaccharide (0111:B4, LPS) intraperitoneally for 24 hours. 2) Preconditioned mice subjected to 0.25 mg/kg LPS followed 24 hour later by 5 mg/kg LPS (LPS/LPS). 3) Control mice (saline vehicle).
Publication Title
Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the Kidney.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
High serum concentrations of kidney-derived protein uromodulin (Tamm-Horsfall protein or THP) have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the kidney and systemically. Consistent with this experimental data, the concentration of circulating THP in patients with surgery-induced acute kidney injury (AKI) correlated with systemic oxidative damage. THP in the serum dropped after AKI, and was associated with an increase in systemic ROS. The increase in oxidant injury correlated with post-surgical mortality and need for dialysis. Mechanistically, THP inhibited the activation of the TRPM2 channel. Furthermore, inhibition of TRPM2 in vivo in a mouse model, mitigated the systemic increase in ROS during AKI and THP deficiency. Our results suggest that THP is a key regulator of systemic oxidative stress by suppressing TRPM2 activity and our findings might help to explain how circulating THP deficiency is linked with poor outcomes and increased mortality.
Publication Title
Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Profiling of MCF-7 cell lines stably overexpressing constitutively active Raf-1, constitutively active MEK, constitutively active c-erbB-2, or ligand-activatable EGFR as models of overexpressed growth factor signaling, as well as control vector transfected cells (coMCF-7) and control vector transfected cells long-term adapted for estrogen-independent growth (coMCF-7/lt-E2).
Publication Title
Activation of mitogen-activated protein kinase in estrogen receptor alpha-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor alpha-negative human breast tumors.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The pancreatic beta cells are the only cells that can produce insulin in response to prevailing glycemia. The development of beta cells was found to be depending on the activity of a complex genetic network. Overexpression of transcriptional factor MafK in beta cells have resulted in impairment of thier functions and suppressed insulin secretion and increased the severity of beta cell loss resulting in an overt diabetes.
Publication Title
β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in rats when administered during early postnatal life. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of genes involved in muscle contraction, pain regulation, and dopaminergic neuronal pathways. First, in agreement with the observed behavioral effects, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified novel genes previously not implicated in acrylamide neurotoxicity that can be further developed into biomarkers for assessing the risk of acrylamide exposure.
Publication Title
Neurobehavioral and transcriptional effects of acrylamide in juvenile rats.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 96 Downloadable Samples
NextSeq500
Description
We utilize gene expression and open chromatin footprinting data to build a gene regulatory network of key transcription factors that capture the cell and time-specific regulatory programs specified during human myeloid differentiation. Overall design: RNA-seq profiling of undifferentiated HL-60, differentiating macrophage, neutrophil, monocyte, and monocyte-derived macrophage cells.
Publication Title
Dynamic Gene Regulatory Networks of Human Myeloid Differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 66 Downloadable Samples
- IlluminaHiSeq1500
Description
The goal of this study is to simultaneously interrogate host and parasite gene expression programs in human macrophages infected with the intracellular parasites from the genus Leishmania. We conducted high-resolution sequencing of the transcriptomes of human macrophages infected with Leishmania spp. using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes at various time points post-infection, enabling us to identify co-expression patterns that correlate with the biology of the parasite and to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. This study provides a solid framework for future functional and genomic studies of leishmaniasis as well as intracellular pathogenesis in general.
Publication Title
Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 7 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy as well as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring.
Publication Title
Effects of moderate drinking during pregnancy on placental gene expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 568 Downloadable Samples
- NextSeq 500
Description
We have developed a computational approach that uses self-organizing maps for integrative genomic analysis. We utilize this approach to identify the single-cell chromatin and transcriptomic profiles during mouse pre-B cell differentiation. Overall design: We use the C1 Fluidigm system to profile gene expression and chromatin accessibility in single-cells during pre-B cell differentiation.
Publication Title
Building gene regulatory networks from scATAC-seq and scRNA-seq using Linked Self Organizing Maps.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 253 Downloadable Samples
- NextSeq 500
Description
We report the application of single-nucleus-based sequencing technology for high-throughput profiling of transcriptome in immortazalized human myoblast KD3. By obtaining over sixty billion bases of sequence from mRNA, we generated comprehensive transcriptome profiles from KD3 undifferentiated myoblast and differentiated multi-nucleated myotube and mono-nucleated cells. We find that the data from single-nucleus RNA-seq is consistent with the transcriptome from single-cell RNA-seq. The pri-mRNA expression characterized by single-nucleus RNA-seq can reflect the actual miRNA level in the whole cell. Overall design: Examination of transcriptome in 1 cell type in 3 differential stages.
Publication Title
Single-nucleus RNA-seq of differentiating human myoblasts reveals the extent of fate heterogeneity.
Sample Metadata Fields
Subject
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