The age groups were used to investigate how gene expression differences between the brachial and the femoral artery effect the heterogeneous atherosclerotic disease initiation and progression.
Gene expression differences in healthy brachial and femoral arteries of Rapacz familial hypercholesterolemic swine.
Age, Specimen part
View SamplesYeast cells were subjected to different combination of the following perturbations: heat stress, myriocin (ISP1) treatment and lipid (myristate) supplement. Then gene expression and lipidomic data were collected under each experimental condition with triplicates.
Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses.
Treatment
View SamplesAstrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients. Overall design: Examination of transcriptome-wide gene expression profiles of purified murine wildtype astrocyte cultures (untreated and treated with IL-6 or EphB1).
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models.
Specimen part, Cell line, Subject
View SamplesAstrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients. Overall design: Examination of transcriptome-wide gene expression profiles of terminally differentiated and enriched iPSC-derived astrocytes harboring the SOD1 D90A mutation
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models.
Specimen part, Subject
View SamplesWe have demonstrated that allergic airway inflammation (induced by an ovalbumin sensitization and aerosol challenge protocol) decreases lung bacterial burden following lung infection with Klebsiella pneumoniae. The goals of this study are to indentify novel targets that are expressed during allergic airway inflammation in this model that contribute to enhanced lung bacterial immunity. Overall design: We isolated total RNA from the lungs of 4 groups of mice at both 0 hours (pre-infection) and 6 hours post-infection. WT and STAT6KO (BALB/c) mice were intraperitoneally sensitzed with alum or ovalbumin (OVA)-alum on day -18. Alum injected mice were not subsequently exposed to OVA aerosol. OVA-alum injected mice underwent aerosol sensitization on days -4, -3, -2, and -1. On day 0, four groups of mice were harvested (pre-infection). These included WT-ALUM, WT-OVA, STAT6KO-ALUM, and STAT6KO-OVA. On day 0, four groups of mice were infected with 10^4cfu of Klebsiella and then lungs were removed at 6 hours post-infection. These groups included WT-ALUM-KP, WT-OVA-KP, STAT6KO-ALUM-KP, and STAT6KO-OVA-KP. The right lung was removed for RNA isolation. Each group contained between 4 and 5 mice.
Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner.
No sample metadata fields
View SamplesHepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis, the final common pathway leading to cirrhosis and liver failure for nearly every cause of chronic liver disease. Activation of HSCs in response to injury represents the key step in hepatic fibrogenesis, and is characterized by a phenotypic change from a non-fibrogenic, quiescent HSC to a fibrogenic HSC myofibroblast that secretes extracellular matrix proteins responsible for the fibrotic scar. We developed a small molecule screen to identify compounds that revert fibrotic human HSC myofibroblasts to an inactive phenotype through the quantification of lipid droplets with fluorescent microscopy. Conditions were optimized in a 384-well format using culture in Matrigel as a positive control. We screened 1600 compounds and identified 30 small molecules that induce reversion to an inactive phenotype. Among the hits, we identified five tricyclic antidepressants (TCAs) and showed that this class of drugs also repressed ACTA2 and COL1A1 while promoting PPAR-gamma expression. RNA sequencing analysis implicated extracellular matrix proteins and the sphingolipid pathway as a target of the TCAs. Overall design: HSCs and HSCs stimulated with TGF-beta were treated with the TCA, nortriptyline or ethanol vehicle for 48 hours. RNA-seq was performed in duplicate for each condition
Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells.
No sample metadata fields
View SamplesWe describe a novel population of human adult cardiac resident stem cells (CRSCs), which are positive for W8B2 antigen, originating from human adult atrial appendages. W8B2+ CRSCs exhibit a spindle-shaped morphology, are clonogenic and able to self-renew. W8B2+ CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2+ CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRa, ISL1 or Wilm’s tumor gene-1 (WT1). W8B2+ CRSCs can differentiate into the cardiovascular lineages and secrete various cytokines. Overall design: Comparative RNA sequencing was performed using W8B2+ cell from human atrial appendages (passage 2 from 3 different patients), c-Kit+ cell from human atrial appendages (passage 2 from 3 different patients) and W8B2+ cell from bone marrow (passage 3 from 2 different patients, from PromoCell, Heidelberg, Germany).
Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart.
No sample metadata fields
View SamplesActivated T cells differentiate into functional subsets which require distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to provide substrate for the tricarboxylic acid cycle and epigenetic reactions and here we identify a key role for GLS in T cell activation and specification. Though GLS-deficiency diminished T cell activation, proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet and Interferon-? expression and CD4 Th1 and CD8 CTL effector cell differentiation. These changes were mediated by differentially altered gene expression and chromatin accessibility, leading to increased sensitivity of Th1 cells to IL-2 mediated mTORC1 signaling. In vivo, GLS-null T cells failed to drive a Th17-mediated Graft-vs-Host Disease model. Transient inhibition of GLS, however, increased Th1 and CTL T cell numbers in viral and chimeric antigen receptor models. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation. Overall design: Cells were treated with glutaminase1 inhibitor or vehicle
Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.
Specimen part, Subject
View SamplesSmall ubiquitin-like modifier (SUMO) family proteins regulate target protein functions by post-translational modification. However, a potent and selective inhibitor to target the SUMO pathway has been lacking. Here we describe ML-792, the first mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, which leads to reduced cancer cell proliferation. Moreover, induction of the MYC oncogene increased the ML-792 mediated viability effect in cancer cells, indicating potential application of SAE inhibitors in MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic subunit (UBA2) mutant S95N/M97T rescued SUMOylation loss and the mitotic defect induced by ML-792, confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins allowing for novel insights into SUMO biology. Overall design: RNA-SEQ was used to analyze changes in mRNA profiles of human colon and breast cancer cells treated with ML00754792 SAEi
Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.
Cell line, Treatment, Subject, Time
View SamplesTumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice there is an influx of tumor macrophages that polarize towards wound repair and immune suppression.
Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
Specimen part, Treatment, Time
View Samples