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GSE24276
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The closure of an open anatomical structure by the directed growth and fusion of two tissue masses is a recurrent theme in mammalian embryology, and this process plays an integral role in the development of the palate, ventricular septum, neural tube, urethra, diaphragm, and eye. In mice, targeted mutations of the genes encoding frizzled1 (Fz1) and frizzled2 (Fz2) show that these highly homologous integral membrane receptors play an essential and partially redundant role in closure of the palate and ventricular septum, and in the correct positioning of the cardiac outflow tract. When combined with a mutant allele of the planar cell polarity (PCP) gene Vangl2 (Vangl2Lp), Fz1 and/or Fz2 mutations also cause defects in neural tube closure and mis-orientation of inner ear sensory hair cells. These observations indicate that frizzled signaling is involved in diverse tissue closure processes, defects in which account for some of the most common congenital anomalies in humans.
Publication Title
Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Telomerase, the essential enzyme that maintains telomere length, contains two core components, TERT and TR. While early studies in yeast and mouse both indicated that loss of telomerase leads to phenotypes that arise after an increased number of generations, due to telomere shortening, recent studies claim additional roles for telomerase components in transcription and the response to DNA damage. To test these telomere length maintenance-independent roles of telomerase components, we examined first generation mTR-/- and mTERT-/- mice with long telomeres. We used gene expression profiling and found no genes that were expressed at significantly different levels when independent mTR-/- G1 mice were compared to mTERT-/- G1 mice and to wild-type mice. In addition, we compared the response to DNA damage in mTR-/-G1 and mTERT-/- G1 mouse embryonic fibroblasts, and found no increase in the response to DNA damage in the absence of either telomerase components compared to wild-type. We conclude that in the wild-type physiological telomere length setting, neither mTR nor mTERT act as a transcription factor or have a role in the DNA damage response.
Publication Title
Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Telomerase, the essential enzyme that maintains telomere length, contains two core components, TERT and TR. While early studies in yeast and mouse both indicated that loss of telomerase leads to phenotypes that arise after an increased number of generations, due to telomere shortening, recent studies claim additional roles for telomerase components in transcription and the response to DNA damage. To test these telomere length maintenance-independent roles of telomerase components, we examined first generation mTR-/- and mTERT-/- mice with long telomeres. We used gene expression profiling and found no genes that were expressed at significantly different levels when independent mTR-/- G1 mice were compared to mTERT-/- G1 mice and to wild-type mice. In addition, we compared the response to DNA damage in mTR-/-G1 and mTERT-/- G1 mouse embryonic fibroblasts, and found no increase in the response to DNA damage in the absence of either telomerase components compared to wild-type. We conclude that in the wild-type physiological telomere length setting, neither mTR nor mTERT act as a transcription factor or have a role in the DNA damage response.
Publication Title
Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
Illumina Genome Analyzer IIx
Description
CCAAT/enhancer binding protein ß (C/EBPß) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPß show protection against excitotoxic and ischemic CNS damage but the involvement of the various C/EBPß expressing cell types in this neuroprotective effect is not solved. Since C/EBPß-deficient microglia show attenuated neurotoxicity in culture we hypothesized that specific C/EBPß deficiency in microglia could be neuroprotective in vivo. In this study we have tested this hypothesis by generating mice with myeloid C/EBPß deficiency. Mice with myeloid C/EBPß deficiency were generated by crossing LysMCre and C/EBPßfl/fl mice . Primary microglial cultures from C/EBPßfl/fl (named here as WT) and LysMCre-C/EBPßfl/fl (named here as KO) mice were treated with lipopolysaccharide ± interferon ? (IFN?) for 6 h and gene expression was analyzed by RNA sequencing. LysMCre-C/EBPßfl/fl mice showed an efficiency of C/EBPß deletion of 100% in cultured microglia. Transcriptomic analysis of C/EBPß-deficient primary microglia revealed C/EBPß-dependent expression of 1068 genes, significantly enriched in inflammatory and innate immune responses GO terms. This study provides new data that support a central role for C/EBPß in the biology of activated microglia. Overall design: LysMCre-C/EBPßfl/fl genotype (12 samples): 4 samples treated with LPS, 4 with LPS +IFNg, and 4 vehicle. C/EBPßfl/fl genotype (9 samples): 3 samples treated with LPS, 3 with LPS +IFNg, and 3 vehicle. Design Case (Treatment LPS or LPS +INF) control (No treatment or vehicle) in LysMCre-C/EBPßfl/fl genotype and in C/EBPßfl/fl genotype
Publication Title
RNA-Seq transcriptomic profiling of primary murine microglia treated with LPS or LPS + IFNγ.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Auxin is a key phytohormone regulating central processes in plants that include embryo development, lateral root growth and flower maturation among others. Auxin is sensed by a set of F-Box proteins of the TIR1/AFB3 family triggering auxin dependent responses by a pathway that involves an interplay between the Aux/IAA transcription repressors and the ARF transcription factors. We have previously shown that the AFB3 auxin receptor has a specific role in coordinating primary and lateral root growth to external and internal nitrate availability (Vidal et al., 2010). In this work, we used an integrated genomics, bioinformatics and molecular genetics approach to dissect regulatory networks acting downstream AFB3 that are activated by a transient nitrate treatment in Arabidopsis roots. Our systems approach unraveled key components of the AFB3 regulatory network leading to changes in lateral root growth in response to nitrate.
Publication Title
Systems approaches map regulatory networks downstream of the auxin receptor AFB3 in the nitrate response of Arabidopsis thaliana roots.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The differentiated state of somatic cells provides barriers for the efficient derivation of induced pluripotent stem cells (iPSCs). To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. This revealed that inhibition of TGF together with activation of Wnt signaling in presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after one week of reprogramming factor expression. In contrast, hepatic progenitors and blood progenitors predominantly required only TGF inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner. We further demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF/MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Together, our observations define novel cell type-specific requirements for the rapid and synchronous reprogramming of somatic cells.
Publication Title
Combinatorial modulation of signaling pathways reveals cell-type-specific requirements for highly efficient and synchronous iPSC reprogramming.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Impaired mitochondrial function has been implicated in the pathogenesis of type 2 diabetes, heart failure and neurodegeneration as well as during aging. Studies with the PGC-1 transcriptional coactivators have demonstrated that these factors are key components of the regulatory network that controls mitochondrial function in mammalian cells. Here we describe a genome-wide coactivation assay to globally identify the transcriptional partners for PGC-1. These analyses revealed a molecular signature of the PGC-1 transcriptional network, and identified BAF60a (Smarcd1), a subunit of the SWI/SNF chromatin-remodeling complex, as a critical regulator of lipid homeostasis. Adenoviral-mediated expression of BAF60a stimulates fatty acid -oxidation in cultured hepatocytes and reduces hepatic triglyceride levels in diet-induced obese mice. BAF60a physically interacts with PGC-1 and is recruited to PPAR target genes in the fasted liver. Liver-specific RNAi knockdown of BAF60a impairs fatty acid oxidation and results in severe hepatic steatosis following starvation. These results define a role for the SWI/SNF complexes in the regulation of hepatic lipid metabolism, and reveal a potential target for therapeutic intervention.
Publication Title
Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 54 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Seasonal influenza outbreaks and recurrent influenza pandemics present major challenges to public health. By studying immunological responses to influenza in different host species, it may be possible to discover common mechanisms of susceptibility in response to various influenza strains. This could lead to novel therapeutic targets with wide clinical application. Using a mouse-adapted strain of influenza (A/HK/1/68-MA20 [H3N2]), we produced a mouse model of severe influenza (p-flu) that reproduces the hallmark high viral load and overexpression of cytokines associated with susceptibility to p-flu in humans. We mapped genetic determinants of the host response using a panel of 29 closely related mouse strains (AcB/BcA panel of recombinant congenic strains) created from influenza-susceptible A/J and influenza-resistant C57BL/6J (B6) mice. Combined clinical quantitative trait loci (cQTL) and lung expression QTL (eQTL) mapping identified candidate genes for two sex-specific QTLs on chromosomes 2 and 17. The former includes the previously described Hc gene, a deficit of which is associated with the susceptibility phenotype in females. The latter includes the phospholipase gene Pla2g7 and Tnfrsf21, a member of the tumor necrosis factor receptor superfamily. Confirmation of the gene underlying the chromosome 17 QTL may reveal new strategies for influenza treatment.
Publication Title
Mapping of clinical and expression quantitative trait loci in a sex-dependent effect of host susceptibility to mouse-adapted influenza H3N2/HK/1/68.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Polycomb repressive complexes (PRCs) are important chromatin regulators of ES cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B, and has been suggested to participate in localizing Polycomb complexes to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Here we have used ES cells conditionally deficient in RYBP to investigate RYBP function. Chromosome immunoprecipitation on a chip (ChIP-chip) of RYBP and microarray experiments were performed using wild type and knocked-out ES cells.
Publication Title
RYBP represses endogenous retroviruses and preimplantation- and germ line-specific genes in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Disease
View Samples