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GSE18507
Mus musculus
14 Downloadable Samples
Description
Trophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (Fgf4, Activin/Nodal/Tgfb) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells we used chromatin immunopreciptiation and DNA microarray analysis (ChIP-chip) to investigate targets of TFs Ap-2g (Tcfap2c), Eomes, Ets2, and Gata3, and a chromatin remodeling factor, Brg1 (Smarca4). We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell self-renewal and pluripotency, co-occupancy of multiple TFs at target genes, and transcriptional regulatory circuitry within the 5 factors. Through genome-wide mapping and global expression analysis of 5 TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Epigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) cells and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails. Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes. Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES cells and TS cells. Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES cells and trichostatin A treated ES cells and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES cell and TS cell self-renewal. By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES cell and TS cell self-renewal.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 54 Downloadable Samples
Description
Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a specific role in oligodendrocyte differentiation we performed time dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the differentiated state where regulated gene sets overlap maximally.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
Description
NOD mice are an inbred strain that display enhanced MZ B cell differentiation from an early age. Interestingly, several lines of evidence implicate MZ B cells in this strain as important contributors to the T cell mediated beta cell destruction associated with the development of type 1 diabetes (T1D). In order to develop a better understanding of the underlying causes for augmented MZ B cell production in NOD mice, we obtained the transcriptional profiles of FO and MZ subsets and TR precursors from NOD mice and compared them to those of the B6 strain.
Publication Title
Intrinsic molecular factors cause aberrant expansion of the splenic marginal zone B cell population in nonobese diabetic mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Endothelin-1 (ET-1) plays a critical role in connective tissue remodeling by fibroblasts during tissue repair and fibrosis. We investigated the molecular pathways in the transmission of ET-1 signals that lead to features of connective tissue remodeling, in particular the role of FAK (focal adhesion kinase).
Publication Title
Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 42 Downloadable Samples
Description
Transcriptome analysis of mRNA samples from a cohort of mice with histopathologically diagnosed Undifferentiated Myeloid Leukemia.
Publication Title
Analyzing tumor heterogeneity and driver genes in single myeloid leukemia cells with SBCapSeq.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 33 Downloadable Samples
Description
Neural tube defects (NTDs) are serious birth defects with an estimated worldwide incidence of 1 per 1,000 live births. The multifactorial nature of NTDs in humans has made it difficult to elucidate pathogenesis mechanisms. However, a strong relationship has been established between folate-homocysteine metabolism and NTD risk. Prevention of a substantial proportion of fetal NTDs can be achieved through maternal folic acid (FA) supplementation. However the mechanism by which FA exerts its beneficial effect remains unclear. METHODS: To improve our understanding of the underlying mechanisms of NTD pathogenesis and the ways in which folate exerts its beneficial effect, we analyzed mRNA profiles as well as folate and vitamin B12 levels in five NTD mouse mutants whose response to dietary FA was previously established. RESULTS: Differentially expressed genes representing the effect of each NTD-causing mutation were identified and associated with biologic pathways. Interestingly, the panel of NTD mutants collectively revealed pathways related to two nuclear receptors, retinoid X receptor (RXR) and pregnane X receptor (PXR), suggesting that these pathways may be related to a shared mechanism of NTD development. Moreover, the NTD-causing mutations that were associated with FA responsiveness had expression profiles that were related to folate-homocysteine metabolic pathways. These pathways were not strongly associated with mutants that do not respond to FA supplementation, implying that FA may be beneficial when the NTD mutation affects pathways related to folate-homocysteine metabolism.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
Description
Affymetrix Mouse Genome 430 2.0 arrays were used to measure genome-wide gene expression levels. The results show that high-risk human papillomavirus oncogenes E6 and E7 reprogram the cervical cancer microenvironment independently of and synergistically with estrogen, a critical co-factor in cervical cancer development and maintenance.
Publication Title
Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 21 Downloadable Samples
Description
To further identify and understand the molecular and immunological correlates of pathology for SARS-CoV infection, we infected 129/S6/SvEv or B129 mice with the TOR2 strain of SARS-CoV. SARS-CoV was detected in the lung and nasal turbinates of infected mice peaking at 1 day post infection (DPI) in both tissues before decreasing rapidly to levels below detection at 7 DPI and 3 DPI, respectively. Pulmonary lesions in virus-infected animals included bronchiolar, peribronchiolar, and perivascular foci of mild to moderate subacute inflammation. Chronic inflammation included inflammatory macrophages, lymphocytes, and plasma cells. Neutralizing antibodies appeared on 5 DPI (IgM); converting to IgG on 7 DPI. Despite the prevailing notion that SARS-CoV interferes with the induction of interferon (IFN) signaling, mice infected with SARS-CoV in vivo demonstrated significantly increased expression of innate antiviral interferon (IFN) response genes (IRGs) in the lungs during the first week of acute infection. By the end of the second week of infection, coordinated expression of MHC class I / II and antigen presentation genes occurred in correlation with declining viral titres. Collectively, the mouse data suggests that robust IFN-driven innate immune responses and a critical shift from innate to adaptive immune responses is necessary for clearance and recovery from SARS-CoV infection.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 13 Downloadable Samples
Description
Pseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherians ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression.
Publication Title
The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome.
Sample Metadata Fields
Sex
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