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GSE28530
Mus musculus
5 Downloadable Samples
Description
DNA methylation of C5-cytosine (5mC) in the mammalian genome is a key epigenetic event that is critical for various cellular processes. However, how the genome-wide 5mC pattern is dynamically regulated remains a fundamental question in epigenetic biology. The TET family of 5mC hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), have provided a new potential mechanism for the dynamic regulation of DNA methylation. The extent to which individual Tet family members contribute to the genome-wide 5mC and 5hmC patterns and associated gene network remains largely unknown. Here we report genome-wide mapping of Tet1 and 5hmC in mESCs and reveal a mechanism of action by which Tet1 controls 5hmC and 5mC levels in mESCs. In combination with microarray and mRNA-seq expression profiling, we identify a comprehensive yet intricate gene network influenced by Tet1. We propose a model whereby Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting the existing 5mC to 5hmC through its enzymatic activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 target loci, thereby providing a new regulatory mechanism for establishing the epigenetic landscape of mESCs, which ultimately contributes to mESC differentiation and the onset of embryonic development.
Publication Title
Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
To examine the role of SPS1 in mammals, we generated a Sps1 knockout mouse and found that systemic SPS1 deficiency was embryonic lethal. Embryos were clearly underdeveloped by E8.5 and virtually reabsorbed by E14.5. Removal of Sps1 specifically in hepatocytes using Albumin-cre preserved viability, but significantly affected expression of a large number of mRNAs involved in cancer, embryonic development and the glutathione system. Particularly notable was the extreme deficiency of glutaredoxin 1 (GLRX1) and glutathione-S-transferase omega 1. To assess these phenotypes at the cellular level, we targeted the removal of SPS1 in F9 cells, a mouse embryonal carcinoma cell line, which recapitulated changes in the glutathione system proteins. We further found that several malignant characteristics of SPS1-deficient F9 cells were reversed, suggesting that SPS1 has a role in supporting and/or sustaining cancer. In addition, the increased ROS levels observed in F9 SPS1/GLRX1 deficient cells were reversed and became more like those in F9 SPS1 sufficient cells by overexpressing mouse or human GLRX1. The results suggest that SPS1 is an essential mammalian enzyme with roles in regulating redox homeostasis and controlling cell growth.
Publication Title
Selenophosphate synthetase 1 is an essential protein with roles in regulation of redox homoeostasis in mammals.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
To identify factors involved in OPC senescence, we compared gene expressions between OPC-CG4, OPC-FCS and OPC-Rev.
Publication Title
Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Dorsomorphin is a small molecule inhibitor of type I bone morphogenic protein receptors (BMPRs). We have found that dorsomorphin affects a wide range of T cell function. In order to obtain the bigger picture of the effects of DM in T cell activation. transcriptomic analysis was performed using mouse primary CD25-CD4+ T cells with either DM (4 M) or vehicle in the presence or absence of stimulation by anti-CD3 and -CD28 antibodies.
Publication Title
Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T-cell activation and differentiation.
Sample Metadata Fields
Specimen part, Treatment
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
- 4 Downloadable Samples
Description
In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, MEF2, and their target genes. Promoter analysis coupled to microarray assay reveals that Klf-binding motifs are highly enriched in the promoter regions of ERK5-dependent upregulated genes. Remarkably, Klf2 and Klf4 expression are also upregulated during differentiation in an ERK5-dependent manner, and knockdown of Klf2 or Klf4 specifically suppresses muscle cell fusion. Moreover, we show that the Sp1 transcription factor links ERK5 to Klf2/4, and that nephronectin, a Klf transcriptional target, is involved in muscle cell fusion. Therefore, an ERK5/Sp1/Klf module plays a key role in the fusion process during skeletal muscle differentiation.
Publication Title
ERK5 regulates muscle cell fusion through Klf transcription factors.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 8 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
To identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression.
Publication Title
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
To identify factors involved in glioma-initiating cells (GICs), we compared gene expression between GIC-like cells and non-GICs.
Publication Title
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Description
Continuous regeneration of digestive enzyme (zymogen) secreting chief cells is a normal aspect of stomach function that is disrupted in pre-cancerous lesions. Regulation of zymogenic cell (ZC) differentiation is poorly understood. Here we profile Parietal, Pit, and Zymogenic cells for comparison and study.
Publication Title
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1.
Sample Metadata Fields
Specimen part
View Samples