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GSE45702
Mus musculus
1 Downloadable Sample
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
S-adenosylmethionine levels regulate the schwann cell DNA methylome.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
DNA methylation is a key epigenetic regulator of mammalian embryogenesis and somatic cell differentiation. Using high-resolution genome-scale maps of methylation patterns, we show that the formation of myelin in the peripheral nervous system, proceeds with progressive DNA demethylation, which coincides with an upregulation of critical genes of the myelination process. More importantly, we found that, in addition to expression of DNA methyltransferases and demethylases, the levels of S-adenosylmethionine (SAMe), the principal biological methyl donor, could also play a critical role in regulating DNA methylation during myelination and in the pathogenesis of diabetic neuropathy. In summary, this study provides compelling evidence that SAMe levels need to be tightly controlled to prevent aberrant DNA methylation patterns, and together with recently published studies on the influence of SAMe on histone methylation in cancer and embryonic stem cell differentiation show that in diverse biological processes, the methylome, and consequently gene expression patterns, are critically dependent on levels of SAMe.
Publication Title
S-adenosylmethionine levels regulate the schwann cell DNA methylome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Methionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
Publication Title
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Journal : Blood. 2009 Jul 9;114(2):469-77. Epub 2009 May 13.
Publication Title
Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
Definitive hematopoietic cells arise from hemogenic endothelium during mid-gestation, indicating a direct link between blood and the endothelial-lined vessels. We sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here we demonstrate that transposon mutagenesis targeting endothelial cells in mice promotes the development of hematopoietic pathologies that are both myeloid and lymphoid in nature. Sequencing of the disrupted genes identified several previously recognized candidate cancer drivers and furthermore revealed that mutations in the lipid kinase Pi4ka can result in myeloid and erythroid dysfunction. Subsequent validation experiments showed that targeted inactivation of the Pi4ka catalytic domain or reduction in mRNA expression inhibited myeloid and erythroid cell differentiation in vitro and promoted anemia in vivo through a mechanism that includes, but it is not limited to deregulation of Akt signaling. Finally, we provide evidence linking PI4KAP2, previously considered a “pseudogene”, with human myeloid and erythroid leukemia. Overall design: mRNA transcriptional comparison between two pieces of spleen from three SBxVEC-Cre+ animals and three control animals to assess clonality of each spleen as a whole.
Publication Title
A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Acquisition and maintenance of vascular smooth muscle fate is essential for the morphogenesis and function of the circulatory system. Loss of contractile properties or changes in the identity of vascular smooth muscle cells (vSMC) can result in structural alterations associated with aneurysms and vascular wall calcifications. Here we report that maturation of sclerotome-derived vSMC is dependent on a transcriptional switch between mouse embryonic days 13 and 14.5. At this time point, Jag1-mediated repression of sclerotome transcription factors Pax1, scleraxis and Sox9 is necessary to fully enable vSMC maturation. Specifically, Notch signaling in vSMC antagonizes sclerotome and cartilage transcription factors, and promotes upregulation of contractile genes. In the absence of Jag1, vSMC acquire a chondrocytic transcriptional repertoire that can lead to ossification of the vascular wall. Importantly, our findings suggest that sustained Notch signaling is essential throughout vSMC life to maintain contractile function, prevent vSMC reprogramming and promote vascular wall integrity. Overall design: mRNA profile of vSMC from the descending aorta of 14.5 embryos Wild type (WT), SMC Jag1-heterozygous (HTZ) and SMC Jag1-null (KO) was generated by deep sequencing, in duplicate.
Publication Title
Repression of Sox9 by Jag1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Acquisition and maintenance of vascular smooth muscle fate is essential for the morphogenesis and function of the circulatory system. Loss of contractile properties or changes in the identity of vascular smooth muscle cells (vSMC) can result in structural alterations associated with aneurysms and vascular wall calcifications. Here we report that maturation of sclerotome-derived vSMC is dependent on a transcriptional switch between mouse embryonic days 13 and 14.5. At this time point, Jag1-mediated repression of sclerotome transcription factors Pax1, scleraxis and Sox9 is necessary to fully enable vSMC maturation. Specifically, Notch signaling in vSMC antagonizes sclerotome and cartilage transcription factors, and promotes upregulation of contractile genes. In the absence of Jag1, vSMC acquire a chondrocytic transcriptional repertoire that can lead to ossification of the vascular wall. Importantly, our findings suggest that sustained Notch signaling is essential throughout vSMC life to maintain contractile function, prevent vSMC reprogramming and promote vascular wall integrity. Overall design: mRNA profile of vascular Smooth Muscle Cells, isolated from the descending aorta of Immorto mouse, treated or not with gamma-secretase inhibitor was generated by deep sequencing, in triplicate.
Publication Title
Repression of Sox9 by Jag1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
We report single cell expression in mouse young and old aorta endothelial cells. These data provide insight in the gene expression related to regeneration of mouse aorta endothelial layer. Overall design: Single cell RNA sequencing was done on a young mouse (8 weeks) and an old mouse (18 months), 10X Genomics Single Cell 3' v2 was used.
Publication Title
Endothelial Regeneration of Large Vessels Is a Biphasic Process Driven by Local Cells with Distinct Proliferative Capacities.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Vascular permeability is frequently associated with inflammation and it is triggered by chemokines and by a cohort of secreted permeability factors, such as VEGF. In contrast, here we showed that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and it is independent of VEGF. Both global and endothelial-specific deletion of PR block physiological vascular permeability in the uterus while misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of genome-wide transcriptional profile of endothelium and ChIP-sequencing revealed that PR induces a NR4A1 (Nur77/TR3) specific transcriptional program that broadly regulates vascular permeability in response to progesterone. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely and venule-specific regulation of vascular barrier function. Silencing NR4A1 blocks PR-mediated permeability responses indicating a direct link between PR and NR4A1. These results reveal a previously unknown function for progesterone receptor on endothelial cell biology with consequences to physiological vascular permeability and implications to the clinical use of progestins and anti-progestins on blood vessel integrity. Overall design: Examination of PR target genes in human umbilical vein endothelial cells (HUVECs) using RNA-seq (PR infected only -PR only and PR infected followed by ligand treatment-PR+P)
Publication Title
Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples