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GSE55304
Mus musculus
12 Downloadable Samples
Description
Perinatal nutritional imbalances may have long-lasting consequences on health and disease, increasing risk of obesity, insulin resistance, type 2 diabetes or cardiovascular disease. This idea has been conceptualized in the Developmental Origins of Health and Disease Hypothesis (DOHaD). In addition, there is evidence that such early-programmed phenotypes can be transmitted to the following generation(s). It is proposed that, environmentally induced, transmission of disease risk is mediated by epigenetic mechanisms.
Publication Title
In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered Lxra DNA methylation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Gene expression changes in mouse skeletal muscle were assessed in wild-type and Jhdm2a null skeletal muscle in an effort to define the role of Jhdm2a in energy expenditure and metabolism.
Publication Title
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation
Publication Title
Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Description
CD25, the high affinity interleukin-2 (IL-2) receptor alpha-chain, is rapidly upregulated by antigen-specific CD8+ T cells after T cell receptor stimulation. We demonstrated that during an acute viral infection, CD25 expression was dynamic, and a subset of virus-specific CD8+ T cells sustained CD25 expression longer than the rest. Examination of the in vivo fate of effector CD8+ T cells exhibiting differential responsiveness to IL-2 revealed that CD25lo cells, which were relatively less sensitive to IL-2, preferentially upregulated CD127 and CD62L and gave rise to the functional long-lived memory pool. In contrast, CD25hi cells that accumulate enhanced IL-2 signals, proliferated more rapidly, were prone to apoptosis, exhibited a more pronounced effector phenotype, and appeared to be terminally differentiated. Sustained IL-2 receptor signaling resulted in increased CD8+ T cell proliferation, higher granzyme B expression and exaggerated contraction after antigen clearance. These data support the hypothesis that prolonged IL-2 signals during priming promote terminal effector differentiation of CD8+ T cells.
Publication Title
Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Maintenance of the blood system is dependent on dormant haematopoietic stem cells (HSCs) with long-term self-renewal capacity. Upon injury these cells are induced to proliferate in order to quickly re-establish homeostasis. The signalling molecules promoting the exit of HSCs out of the dormant stage remain largely unknown. Here we show that in response to treatment of mice with interferon-alpha (IFN), HSCs efficiently exit G0 and enter an active cell cycle. HSCs respond to IFN treatment by increased phosphorylation of STAT1 and PKB/Akt, expression of IFN target genes and up-regulation of stem cell antigen-1 (Sca-1). HSCs lacking either the interferon-/ receptor (IFNAR), STAT1 or Sca-1 are insensitive to IFN stimulation, demonstrating that STAT1 and Sca-1 mediate IFN induced HSC proliferation. Although dormant HSCs are resistant to the anti-proliferative chemotherapeutic agent 5-FU1, HSCs pre-treated (primed) with IFN and thus induced to proliferate are efficiently eliminated by 5-FU exposure in vivo. Conversely, HSCs chronically activated by IFN are functionally compromised and are rapidly out competed by non-activatable IFNAR-/- cells in competitive repopulation assays. In summary, while chronic activation of the IFN pathway in HSCs impairs their function, acute IFN treatment promotes the proliferation of dormant HSCs in vivo. These data may help to clarify the so far unexplained clinical effects of IFN on leukemic cells and raise the possibility for novel applications of type I interferons to target cancer stem cells.
Publication Title
IFNalpha activates dormant haematopoietic stem cells in vivo.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 2 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Polycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved at least partly through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Although recent studies have revealed the genome wide binding patterns of some of the PRC1 and PRC2 components, as well as the H3K27me3 mark, there have been no reports describing genome wide localization of uH2A. Using the recently developed ChIP-Seq technology, here we report genome wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We provide evidence to suggest that DNA methylation is tightly linked to H2A ubiquitylation in high density CpG promoters. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells.
Publication Title
Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Obesity is often associated with a low-grade systemic inflammation state that contributes to the development of insulin resistance and atherosclerotic complications. This is usually coupled with increased macrophage infiltration in the adipose tissue and a defect in adipocyte differentiation that results in accumulation of hypertrophic fat cells characterized by a deregulated pattern of adipokine expression. Here we show that knockdown of histone demethylase lsd1 in 3T3-L1 preadipocytes results in defective adipogenesis and derepression of an inflammatory program in these cells.
Publication Title
Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Epithelial tumor cells (E) underwent EMT in vivo in FVB/N mice generating mesenchymal tumors. Mesenchymal cell lines (M1-M4) were each derived from a different mouse. This study compares gene expression between these two different tumor types.
Publication Title
Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Normal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes.
Publication Title
Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
Sample Metadata Fields
No sample metadata fields
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