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SRP068103
Mus musculus
16 Downloadable Samples
Illumina HiSeq 2000
Description
The FBXL10 protein (also known as KDM2B, JHDM1B, CXXC2, and NDY1) is bound to essentially all CpG-rich promoters in the mammalian genome. FBXL10 is expressed as two isoforms: FBXL10-1, a longer form that contains an N-terminal JmjC domain with C- terminal F-box, CXXC, PHD, RING, and leucine rich repeat (LRR) domains, and FBXL10-2, a shorter form that initiates at an alternative internal exon and which lacks the JmjC domain but retains the other domains. Selective deletion of Fbxl10-1 had been reported to produce a minor and variable phenotype, and most mutant animals were essentially normal. We show here that deletion of Fbxl10-2 (in a manner that does not perturb expression of Fbxl10-1) resulted in a very different phenotype with craniofacial abnormalities, greatly increased lethality, and female sterility in surviving homozygous mutants. The phenotype of the Fbxl10-2 deletion was more severe in female mutants. We found that mutants that lacked both FBXL10-1 and -2 showed embryonic lethality and even more extreme sexual dimorphism, with more severe gene dysregulation in mutant female embryos. X-linked genes were most severely dysregulated, and there was marked overexpression of Xist in mutant females although genes that encode factors that bind to Xist RNA were globally down-regulated in mutant female as compared to male embryos. FBXL10 is the first factor shown to be required both for the normal expression and function of the Xist gene. Overall design: Expression analysis using RNA-seq was performed on WT and Fbxl10T/T male and female embryos.
Publication Title
Abnormal X chromosome inactivation and sex-specific gene dysregulation after ablation of FBXL10.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
- NextSeq 500
Description
Three different progenitor cell subsets in subcutaneous and visceral adipose tissues derived from 5 obese patients were subjected to AmpliSeq transcriptome profiling. Transcriptomic profiles were analyzed to compare progenitor cell subsets and the impact of subcutaneous and visceral adipose tissue location. Overall design: Transcriptomic profiling of 3 different progenitor cell types in subcutaneous and visceral adipose tissues derived from 5 obese patients (3X2X5=30 samples).
Publication Title
Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recombinant baculoviral vectors efficiently transduce several types of cells in the brain. To characterize host responses to viral challenge, thus verifying the suitability of using the virus for the development of gene therapy strategies in the central nervous system, we used cDNA microarray technology to examine in vitro and in vivo global cellular gene expression profiles after viral transduction. We demonstrated that the transduction induced host antiviral responses as a major reaction in all three types of samples profiled, including the rat brain, cultured human astrocytes and human neuronal cells. The related genes were mainly those associated with innate immunity. Several genes of the major histocompatibility complex molecules, an important component of the host adaptive immunity to exogenous pathogens, were up-regulated in the rat brain and human astrocytes, but not in neuronal cells. We also observed that genes related to cell death and apoptosis were up-regulated and genes related cell cycle regulation were down-regulated in neuronal cells, but not obviously affected in astrocytes. These findings should be useful in understating the molecular basis for neural cell response to baculoviral transduction and guiding rational applications of baculoviral vectors in the central nervous systems
Publication Title
Gene expression profiling to define host response to baculoviral transduction in the brain.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Analysis of gene expression in pathologically confirmed glioblastoma (GBM) samples. These data were used to test a classifier that was generated to distinguish GBM tumor samples with loss of neurofibromin 1 (NF1) function
Publication Title
A machine learning classifier trained on cancer transcriptomes detects NF1 inactivation signal in glioblastoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from 18-month-old Ahr-knockout and wild-type mice. HSC from aged AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.
Publication Title
Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Achievement of specific tumor cell targeting remains a challenge for glioma gene therapy. We report here the identification and characterization of a 5 sequence of human HMGB2 gene for transcriptional targeting to glioblastoma. We performed microarray analysis and found HMGB2 as one of the genes that had a low level of expression in normal human astrocytes, but was significantly up-regulated in glioblastoma cells. Real-time PCR quantification revealed increase in HMBG2 expression level in glioblastoma tissues and cells between 11 to 79 fold over that in normal human brain tissue. With progressive truncation of a 5-upstream sequence of the HMGB2 gene, we identified a 500-bp fragment that displayed a high transcriptional activity in glioblastoma cells, but a low activity in normal brain cells. Using the sequence to drive the expression of the herpes simplex virus thymidine kinase gene in the context of a baculoviral vector, glioblastoma cells died in the presence of ganciclovir, whereas normal human astrocytes and neurons were not affected. We further confirmed that after intra-tumor injection, the baculoviral vector effectively suppressed the growth of human glioblastoma cells in a mouse xenograft model. Our results suggest that the 5-upstream sequence of the HMGB2 gene can be used as an efficient, tumor-selective promoter in targeted vectors for glioblastoma gene therapy.
Publication Title
High mobility group box2 promoter-controlled suicide gene expression enables targeted glioblastoma treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
Hoxb8 mutant mice show compulsive behavior similar to trichotillomania, a human obsessive-compulsive-spectrum disorder. The only Hoxb8 lineage-labeled cells in the brains of mice are microglia, suggesting that defective Hoxb8 microglia caused the disorder. What is the source of the Hoxb8 microglia? It has been posited that all microglia progenitors arise at embryonic day (E) 7.5 during yolk sac hematopoiesis, and colonize the brain at E9.5. In contrast, we show the presence of two microglia subpopulations: canonical, non-Hoxb8 microglia and Hoxb8 microglia. Unlike non- Hoxb8 microglia, Hoxb8 microglia progenitors appear to be generated during the second wave of yolk sac hematopoiesis, then detected in the aorto-gonad-mesonephros (AGM) and fetal liver, where they are greatly expanded, prior to infiltrating the E12.5 brain. Further, we demonstrate that Hoxb8 hematopoietic progenitor cells taken from fetal liver are competent to give rise to microglia in vivo. Although the two microglial subpopulations are very similar molecularly, and in their response to brain injury and participation in synaptic pruning, they show distinct brain distributions which might contribute to pathological specificity. Non-Hoxb8 microglia significantly outnumber Hoxb8 microglia, but they cannot compensate for the loss of Hoxb8 function in Hoxb8 microglia, suggesting further crucial differences between the two subpopulations. Overall design: Green (non-Hoxb8, control) and yellow (Hoxb8, experimental) microglia data sets
Publication Title
Correction: Two distinct ontogenies confer heterogeneity to mouse brain microglia (doi: 10.1242/dev.152306).
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 1000
Description
Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30?/?), we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding g-Sarcoglycan (SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the cerebrovascular Sarcoglycan complex (SGC) and showed the presence of a-, ß-, d-, ?-, e- and ?- SG, as well as Sarcospan. Altogether, our results suggest that the Sarcoglycan complex is present in the cerebrovascular system, and that expression of one of its members, g-Sarcoglycan, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions. Overall design: Comparison of 3-month-old Cx30 deleted mice against WT genetic background.
Publication Title
The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Biallelic inactivating mutations of the transcription factor 1 gene (TCF1), encoding hepatocyte nuclear factor 1a (HNF1a), were identified in 50% of hepatocellular adenomas (HCA) phenotypically characterized by a striking steatosis. To understand the molecular basis of this aberrant lipid storage, we performed a microarray transcriptome analysis validated by quantitative RT-PCR, western-blotting and lipid profiling. In mutated HCA, we showed a repression of gluconeogenesis coordinated with an activation of glycolysis, citrate shuttle and fatty acid synthesis predicting elevated rates of lipogenesis. Moreover, the strong dowregulation of L-FABP suggests that impaired fatty acid trafficking may also contribute to the fatty phenotype. In addition, transcriptional profile analysis of the observed deregulated genes in non-HNF1a-mutated HCA as well as in non-tumor livers allowed us to define a specific signature of the HNF1a-mutated HCA. In theses tumors, lipid composition was dramatically modified according to the transcriptional deregulations identified in the fatty acid synthetic pathway. Surprisingly, lipogenesis activation did not operate through SREBP-1 and ChREBP that were repressed. We conclude that steatosis in HNF1a-mutated HCA results mainly from an aberrant promotion of lipogenesis that is linked to HNF1a inactivation and that is independent of both SREBP-1 and ChREBP activation. Finally, our findings have potential clinical implications since lipogenesis can be efficiently inhibited by targeted therapies.
Publication Title
HNF1alpha inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
In support of our manuscript investigating the roles of ILCs and T cells in the maintenance of gut hoemostasis, we have performed RNAseq on terminal illeum of mice lacking either all adaptive immune cells (RAG1 -/-), deficient in T cells (TCRalpha -/-), or deficient in T cells but co-housed with wild-type mice and RAG1 -/- mice. Overall design: Tissues from three mice per group were analysed, and the following comparisions were made: RAG1-/- vs. WT C57BL/6 and TCRa-/- co-housed vs TCRa-/- seperately housed. Differential expression genes were identified at 1% FDR using DESeq2.
Publication Title
Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism.
Sample Metadata Fields
Subject
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