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GSE55525
Mus musculus
71 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comprehensive analysis of gene expression in hematopoietic stem and progenitor cells from young and old mice.
Publication Title
Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene Expression profiling of HSCs isolated at different stages of ontogeny to address correlation between gene expression and changes in DNA methylation
Publication Title
Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus, Rattus norvegicus
- 5 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
SV40 transforms cells through the action of two oncoproteins, large T antigen and small t antigen. Small t antigen targets phosphatase PP2A, while large T antigen stimulates cell proliferation and survival by action on multiple proteins, including the tumor suppressors Rb and p53. Large T antigen also binds components of the transcription initiation complex and several transcription factors. We examined global gene expression in SV40-transformed mouse embryo fibroblasts, and in enterocytes obtained from transgenic mice. SV40 transformation alters the expression of approximately 800 cellular genes in both systems. Much of this regulation is observed in both MEFs and enterocytes and is consistent with T antigen action on the Rb-E2F pathway. However, the regulation of many genes is cell-type specific, suggesting that unique signaling pathways are activated in different cell types upon transformation, and that the consequences of SV40 transformation depends on the type of cell targeted.
Publication Title
Cell-type specific regulation of gene expression by simian virus 40 T antigens.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized.
Publication Title
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
DNA methylation is a mechanism of epigenetic regulation that is common to all vertebrates. Functional studies support its relevance for tissue homeostasis, but the global dynamics of DNA methylation during in vivo differentiation have not been worked out in detail. Here we report high-resolution DNA methylation maps of adult stem cell differentiation in mouse, focusing on 19 purified cell populations of the blood and skin lineages. Except for global demethylation in erythrocytes, observed DNA methylation changes were locus-specific and relatively modest in size. They frequently overlapped with lineage-associated transcription factors and their binding sites, suggesting that DNA methylation may protect cells from aberrant transcription factor activation. DNA methylation and gene expression provided highly complementary information, and combining the two enabled us to infer the blood lineage hierarchy directly from genomic data. In summary, our dataset and analysis demonstrate that in vivo differentiation of adult stem cells is associated with small but informative changes in the distribution of DNA methylation across the mouse genome.
Publication Title
DNA methylation dynamics during in vivo differentiation of blood and skin stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have shown that Sox10 plays a crucial role in the initiation and maintenance of giant congenital nevi and melanoma in a mouse model of melanoma.To dissect the molecular mechanisms and analyze the role of SOX10 in the maintenance of human melanoma, we have performed microarray study.
Publication Title
Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDLs ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathways potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDLs major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-Ideficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.
Publication Title
High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
IlluminaHiSeq2000
Description
In contrast to urodele amphibians and teleost fish, mammals lack the regenerative responses to replace large body parts. Amphibian and fish regeneration uses dedifferentiation, i.e. reversal of differentiated state, as a means to produce progenitor cells to eventually replace damaged tissues. Therefore, activation of dedifferentiation response in mammalian tissues holds an immense promise for human regenerative medicine. msx2 expression has been shown to peak at the early time points of amphibian limb regeneration. Despite this temporal importance in the heterogenous regenerating limb tissues, the potential role of msx2 in dedifferentiation was previously not addressed in salamander or mammalian muscle cells. In order to test this, we ectopically overexpressed msx2 in mammalian myotubes and profiled their transcriptomes using next generation sequencing. We identified 4964 up-regulated and 4464 down-regulated transcripts in myotubes compared to myoblasts (uninduced GFP control cells; = 1.5 fold; FDR corrected p-values < 0.01). Upon ectopic msx2 expression in myotubes, 923 transcripts were downregulated, whereas 1283 transcripts were upregulated. Based on msx2's potential role in dedifferentiation, we reasoned that the transcripts, which are normally upregulated in myotubes in comparison to myoblasts, should go down upon msx2-expression. In accord with this idea, 575 myotube-enriched transcripts were downregulated after one day of ectopic msx2 expression. Similarly, 331 myoblast-enriched transcripts were upregulated upon msx2 expression. Overall design: To extensively analyze transcriptome-wide changes upon ectopic msx2 expression in mammalian myotubes, we performed next generation RNA-sequencing (RNA-seq) on uninduced and induced isolated myotubes that have msx2 and GFP or GFP alone transgenes. As a reference for the undifferentiated state, we also sequenced the transcriptomes of uninduced myoblast cultures of these two transgenic constructs. Deep sequencing was performed using Illumina HiSeq.
Publication Title
Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
see Super Series Summary Overall design: We treated Drosophila S2-DRSC cells for 1, 2, 4 and 20 h with 10 µM JQ1 and compared their gene expression to DMSO-treated control cells (1 and 20 h).
Publication Title
The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Endothelial cells (EC) lining arteries and veins have distinct molecular and functional signatures. The (epi)genetic regulatory mechanisms underlying this heterogeneity in human EC are incompletely understood. Using genome-wide microarray screening we established a specific fingerprint of freshly isolated arterial (HUAEC) and venous EC (HUVEC) from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions and pathways. Among the arterial genes were 8 transcription factors, including HEY2, a downstream target of Notch signaling and the current golden standard pathway for arterial EC specification. Short-term culture of HUAEC or HUVEC abrogated differential gene expression resulting in a default state. Erasure of arterial gene expression was at least in part due to loss of canonical Notch activity and HEY2 expression. Notably, nCounter analysis revealed that restoring HEY2 expression or Delta-like 4 (Dll4)-induced Notch signaling in cultured HUVEC or HUAEC only partially reinstated the arterial EC gene signature while combined overexpression of the 8 transcription factors restored this fingerprint much more robustly. Each transcription factor had a different impact on gene regulation, with some stimulating only few and others boosting a large proportion of arterial genes. Interestingly, although there was some overlap and cross-regulation, the transcription factors largely complemented each other in regulating the arterial EC gene profile. Thus, our study showed that Notch signaling determines only part of the arterial EC signature and identified additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity
Publication Title
Unraveling a novel transcription factor code determining the human arterial-specific endothelial cell signature.
Sample Metadata Fields
Specimen part
View Samples