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GSE82269
Homo sapiens
6 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Bone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor- (TNF-) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.
Publication Title
Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.
Sample Metadata Fields
Sex, Specimen part, Race, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of this study was to identify lncRNAs and novel transcripts that are differentially regulated in cutaneous squamous cell carcinoma (SCC) using RNA sequencing
Publication Title
Cancer-Associated Long Noncoding RNA SMRT-2 Controls Epidermal Differentiation.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
NextSeq 500
Description
Despite the prevalence and recognition of its detrimental impact, clinical complications of sepsis remain a major challenge. Here, we investigated the effects of myeloid ferritin heavy chain (FtH) in regulating the pathogenic sequelae of sepsis. We demonstrate that deletion of myeloid FtH leads to tolerance towards sepsis as evidenced by reduced serum cytokine levels, multi-organ dysfunction and subsequent mortality. We identified that such tolerance is predominantly mediated by the compensatory increase in circulating ferritin (ferritin light chain; FtL) in the absence of myeloid FtH. Our in vitro and in vivo studies indicate that prior exposure to ferritin provides significant tolerance to the septic process by restraining an otherwise dysregulated response to infection. These findings are mediated by an inhibitory action of ferritin on NF-?B activation and its downstream effects. Taken together, our findings suggest an essential immunomodulatory function for circulating ferritin and enhances our understanding of this acute phase reactant. Overall design: Total RNA were isolated from blood leukocytes of wild type FtH mice and Myeloid deficient FtH mice following sham and CLP surgery. Three biological replicates were considered for each genotype and surgery type.
Publication Title
Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury.
Sample Metadata Fields
Cell line, Subject
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Cardiomyopathy in type 1 diabetic patients is characterized by early onset diastolic and late onset systolic dysfunction. The mechanism underlying development of diastolic and systolic dysfunction in diabetes remains unknown.
Publication Title
Activation of a novel long-chain free fatty acid generation and export system in mitochondria of diabetic rat hearts.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Ixodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kinetics of tick-borne viral transmission, this modulation must occur as early as tick attachment and initiation of feeding. In this study, the gene expression profile of cutaneous bite-site lesions created by uninfected ticks were analyzed at 1, 3, 6, and 12 hours after Ixodes scapularis nymphal tick attachment to discover host pathways or responses potentially important in tick-borne viral establishment.
Publication Title
Early immunologic events at the tick-host interface.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ablation of the mouse gene for Onecut-2 was reported previously, but characterization of the resulting knockout mice was focused on in utero development, principally embryonic development of liver and pancreas. Here, we examine postnatal development of these Onecut-2 knockout mice, especially the critical period prior to weaning. Microarray technology was used to determine the effect of Onecut-2 ablation on gene expression in duodenum, whose epithelium has among the highest levels of Onecut-2. A subset of intestinally expressed genes showed dramatically altered patterns of expression. Many of these genes encode proteins associated with the epithelial membrane, including many involved in transport and metabolism. Previously, we reported that Onecut-2 was critical to temporal regulation of the adenosine deaminase gene in duodenum. Many of the genes with altered patterns of expression in the Onecut-2 knockout mouse duodenum displayed changes in the timing of gene expression.
Publication Title
Onecut-2 knockout mice fail to thrive during early postnatal period and have altered patterns of gene expression in small intestine.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cardiac hypertrophy is regulated by the zinc finger-containing DNA binding factors Gata4 and Gata6, both of which are required to mount a productive growth response of the adult heart. To determine if Gata4 and Gata6 are redundant or have non-overlapping roles, we performed cardiomyocyte-specific conditional gene deletions for Gata4 and Gata6 in conjunction with reciprocal replacement with a transgene encoding either Gata4 or Gata6, during the pressure overload response. We determined that Gata4 and Gata6 play a redundant and dosage-sensitive role in programming the hypertrophic growth response itself following pressure overload stimulation. However, non-redundant functions were identified as functional decompensation induced by either Gata4 or Gata6 deletion was not rescued by the reciprocal transgene, and only Gata4 heart-specific deletion produced a reduction in capillary density after pressure overload. Gene expression profiling from hearts of these gene-deleted mice showed both overlapping and unique transcriptional codes, with Gata4 exhibiting the strongest impact. These results indicate that Gata4 and Gata6 play a dosage-dependent and semi-redundant role in programming cardiac hypertrophy, but that each has a unique role in maintaining cardiac homeostasis and adaptation to injury that cannot be compensated by the other.
Publication Title
Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
In order to identify targets for HDAC4, NRVM were infected with adenoviral vectors encoding beta-Galactosidase or Flag- HDAC4, and incubated in serum free or 10% fetal calf serum containing growth medium for 48 hrs.
Publication Title
Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Rationale: Monitoring and controlling cardiomyocyte activity with optogenetic tools offers exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac excitation from the cellular to the whole heart level. Objective: To test the hypothesis that cardiomyocyte-targeted voltage-sensitive fluorescence protein 2.3 (VSFP2.3) can be exploited as optogenetic tool for the monitoring of electrical activity in isolated cardiomyocytes and the whole heart as well as function and maturity in induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Methods and Results: We first generated mice with cardiomyocyte-restricted expression of VSFP2.3 and demonstrated distinct sarcolemmal localization of VSFP2.3 without any signs for associated pathologies (assessed by echocardiography). Optically recorded VSFP2.3 signals correlated well with membrane voltage measured simultaneously by patch-clamping. The utility of VSFP2.3 for human action potential recordings was confirmed by simulation of immature and mature action potentials in murine VSFP2.3 cardiomyocytes. Optical cardiograms (OCGs) could be monitored in whole hearts ex vivo and minimally invasively in vivo via fiber optics at physiological heart rate (10 Hz) and under pacing-induced arrhythmia. Finally, we reprogrammed tail-tip fibroblasts from transgenic mice and used the VSFP2.3 sensor for benchmarking functional and structural maturation in iPSC-derived cardiomyocytes. Conclusions: We introduce a novel transgenic voltage-sensor model as a new method in cardiovascular research and provide proof-of-concept for its utility in optogenetic sensing of physiological and pathological excitation in mature and immature cardiomyocytes in vitro and in vivo. Overall design: Determination of transgene (VSFP2.3) cardiotoxicity
Publication Title
Sensing Cardiac Electrical Activity With a Cardiac Myocyte--Targeted Optogenetic Voltage Indicator.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The beta1-adrenergic receptor (beta1AR; ADRB1) polymorphism Arg 389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that beta1-Arg389 and beta1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wildtype and transgenic mice that expressed either human beta1-Arg389 and beta1-Gly389 receptors, or AC5 adenyl cyclase, sampling at an early age and stage, prior to the onset of pathologic features. We observed substantial overlap of dysregulated genes across all three transgenic heart models, consistent with a shared coupling to cAMP-dependent regulation of cardiac processes and adaptive responses. All three models up-regulated genes associated with RNA metabolism and translation, and down-regulated genes associated with mitochondria and energy metabolism, consistent with cAMP-driven increase in cardiac contractility, protein synthesis, and compensatory down-regulation of mitochondrial energy production. Both beta1AR transgenics activated additional genes associated with kinase-dependent pathways, and uniquely, beta1-Arg389 hearts caused up-regulation of genes associated with inflammation, programmed cell death, and extracellular matrix. These results substantially expand the scope of 7-transmembrane domain receptor signaling propagation beyond known cognate G-protein couplings. Moreover, they implicate alterations of a repertoire of processes evoked by a single amino acid variation in the cardiac beta1AR that might be exploited for genotype-specific heart failure diagnostics and therapeutics.
Publication Title
Differential coupling of Arg- and Gly389 polymorphic forms of the beta1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs.
Sample Metadata Fields
No sample metadata fields
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