To determine whether an accelerated aging-like phenotype occurs in hematopoiesis of young Tif1?-/- mice (4 months old), we purified 200,000 hematopoietic stem cells (LSK: Lineage negative, Sca1+, c-Kit+) from Tif1?-/- mice and performed high-throughput mRNA sequencing (RNA-seq). We compared this transcriptome to physiological aging by creating two other RNAseq libraries from young (4 months old) and old (20 months old) wild type mice. Overall design: RNAseq study on young Tif1?-/- mice (4 months old), young wild type mice (4 months old) and old wild type mice (20 months old).
Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
No sample metadata fields
View SamplesWe report that the HF/HS-mediated functional enrichment of genes of immunity and inflammation is driven toward normal by the AOF supplementation Obesity may not constantly associate with metabolic disorders and mortality later in life, raising the challenging concept of healthy obesity. Here, high fat-high sucrose (HF/HS) feeding produces hyperglycaemia and hypercholesterolemia, increases oxidative stress, elevates endotoxemia, expands adipose tissue (with enlarged adipocytes, macrophage infiltration and accumulation of cholesterol and oxysterols), and reduces lifespan of obese mice. Despite persistence of obesity, supplementation with an antioxidant formulation normalizes plasma lipids and endotoxemia, prevents macrophage recruitment in adipose tissue, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends lifespan. The HF/HS-mediated functional enrichment of genes of immunity and inflammation (in particular response to lipopolysaccharides) is driven towards normal by the antioxidant formulation. It is concluded that the limitation of immune cell infiltration in adipose tissue on the long term by an antioxidant formulation can increase lifespan independently of body weight and fat storage. It constitutes the hallmark of a healthy adiposity trait. Overall design: Examination of the expression profile of mice adipose tissues fed either standard (Std), High-fat/high-sucrose (HF/HS) or HF/HS + antioxidant formulation (AOF) for 180 days
Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract.
Age, Specimen part, Cell line, Subject
View SamplesIdentification of genetic polymorphisms associated with inter-individual variation in immune response to Mycobacterium tuberculosis infection.
Deciphering the genetic architecture of variation in the immune response to Mycobacterium tuberculosis infection.
Sex
View SamplesWe applied a novel approach of parallel transcriptional analysis of multiple, highly fractionated stem and progenitor populations in a genetically defined subset of AML (AML with monosomy 7). We isolated phenotypic long-term HSC (LT-HSC), short-term HSC (ST-HSC), and committed granulocyte-monocyte progenitors (GMP) from individual patients with AML, and measured gene expression profiles of each population, and in comparison to their phenotypic counterparts from age-matched healthy controls.
Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS.
Age, Specimen part
View SamplesWe applied a novel approach of parallel transcriptional analysis of multiple, highly fractionated stem and progenitor populations from patients with acute myeloid leukemia (AML) and a normal karyotype. We isolated phenotypic long-term HSC (LT-HSC), short-term HSC (ST-HSC), and committed granulocyte-monocyte progenitors (GMP) from individual patients, and measured gene expression profiles of each population, and in comparison to their phenotypic counterparts from age-matched healthy controls.
Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS.
Age, Specimen part
View SamplesDNA methylation is an epigenetic mark thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells with a live pathogenic bacteria is associated with rapid changes in methylation levels at thousands of loci. We performed an integrated analysis of data on genome-wide DNA methylation, histone mark patterns, chromatin accessibility, and gene expression, before and after infection. We found that infection-induced changes in methylation rarely occur at promoter regions and instead localize to distal enhancer elements. Active demethylation is associated with extensive epigenetic remodeling, including the gain of histone activation marks and the induction of enhancer RNAs, and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that active, rapid changes in DNA methylation in enhancers play a previously unappreciated role in regulating the transcriptional response of immune cells to infection. Overall design: Transcriptional profiles (polyA+) of 6 non-infected and 6 MTB-infected dendritic cell samples.
Bacterial infection remodels the DNA methylation landscape of human dendritic cells.
No sample metadata fields
View SamplesAstrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring in vitro neural stem cell properties. In order to identify novel regulators of this astrocyte subset, we performed a genome-wide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the adult mouse cerebral cortex. The expression pattern was compared with astrocytes from normal cortex and adult neural stem cells isolated from the sub-ependymal zone (GSE18765). These comparisons revealed a set of genes up-regulated both in neurogenic neural stem cells and reactive astrocytes, including the lectins Galectin-1 and -3. These results, as well as the pattern of Galectin expression in the lesioned brain, led us to examine the functional significance of these lectins in brains of Galectin-1/3 double-knockout mice.
Astrocyte reactivity after brain injury-: The role of galectins 1 and 3.
Sex, Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Cell line, Treatment
View SamplesThe indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favored development of epigenetic drugs. In this study, we have design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of hematological neoplasia (Acute Myeloid Leukemia-AML, Acute Lymphoblastic Leukemia-ALL and Diffuse Large B-cell Lymphoma-DLBCL) with the lead compound CM-272, inhibited cell proliferation and promoted apoptosis, inducing interferon stimulated genes and immunogenic cell death. CM-272 significantly prolonged survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series, as a promising therapeutic tool for unmet needs in hematological tumors.
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis.
Specimen part, Disease
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