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Homo sapiens
4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Expression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.
Publication Title
A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
Illumina HiSeq 3000
Description
Reduced eukaryotic Initiation Factor 2 (eIF2)a phosphorylation (p-eIF2a) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2a has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2a in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2a in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ?FosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2a and the gateway drug properties of psychoactive cannabinoids. Overall design: RNAseq from PC12 cell line with a 6 hour DMSO or WIN treatment.
Publication Title
Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Skeletal muscle atrophy is a debilitating condition associated with weakness, fatigue, and reduced functional capacity. Nuclear factor-kappaB (NF-B) transcription factors play a critical role in atrophy. Knockout of genes encoding p50 or the NF-B co-transactivator, Bcl-3, abolish disuse atrophy and thus they are NF-B factors required for disuse atrophy. We do not know however, the genes targeted by NF-B that produce the atrophied phenotype. Here we identify the genes required to produce disuse atrophy using gene expression profiling in wild type compared to Nfkb1 (gene encodes p50) and Bcl-3 deficient mice. There were 185 and 240 genes upregulated in wild type mice due to unloading, that were not upregulated in Nfkb1-/- and Bcl-3-/- mice, respectively, and so these genes were considered direct or indirect targets of p50 and Bcl-3. All of the p50 gene targets were contained in the Bcl-3 gene target list. Most genes were involved with protein degradation, signaling, translation, transcription, and transport. To identify direct targets of p50 and Bcl-3 we performed chromatin immunoprecipitation of selected genes previously shown to have roles in atrophy. Trim63 (MuRF1), Fbxo32 (MAFbx), Ubc, Ctsl, Runx1, Tnfrsf12a (Tweak receptor), and Cxcl10 (IP-10) showed increased Bcl-3 binding to B sites in unloaded muscle and thus were direct targets of Bcl-3. p50 binding to the same sites on these genes either did not change or increased, supporting the idea of p50:Bcl-3 binding complexes. p65 binding to B sites showed decreased or no binding to these genes with unloading. Fbxo9, Psma6, Psmc4, Psmg4, Foxo3, Ankrd1 (CARP), and Eif4ebp1 did not show changes in p65, p50, or Bcl-3 binding to B sites, and so were considered indirect targets of p50 and Bcl-3. This work represents the first study to use a global approach to identify genes required to produce the atrophied phenotype with disuse.
Publication Title
Identification of genes that elicit disuse muscle atrophy via the transcription factors p50 and Bcl-3.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice.
Publication Title
The ChIP-seq-defined networks of Bcl-3 gene binding support its required role in skeletal muscle atrophy.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-B, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. A LIF blocking antibody abolished C26 CM-induced STAT reporter activation STAT3 phosphorylation and myotube atrophy, but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked the C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3C-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together these data support an important role of LIF- JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.
Publication Title
A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Existing data suggest that NF-kappaB signaling is a key regulator of cancer-induced skeletal muscle wasting. However, identification of the components of this signaling pathway and of the NF-B transcription factors that regulate wasting is far from complete. In muscles of C26 tumor bearing mice, overexpression of d.n. IKK blocked muscle wasting by 69%, the IB-super repressor blocked wasting by 41%. In contrast, overexpression of d.n. IKK or d.n. NIK did not block C26-induced wasting. Surprisingly, overexpression of d.n. p65 or d.n. c-Rel did not significantly block muscle wasting. Genome-wide mRNA expression arrays showed upregulation of many genes previously implicated in muscle atrophy. To test if these upregulated genes were direct targets of NF-B transcription factors, we compared genome-wide p65 or p50 binding to DNA in control and cachectic muscle using ChIP-sequencing. Bioinformatic analysis of ChIP-seq data from control and C26 muscles showed increased p65 and p50 binding to a few regulatory and structural genes but only two of these genes were upregulated with atrophy. The p65 and p50 ChIP-seq data are consistent with our finding of no significant change in protein binding to an NF-B oligo in a gel shift assay. Taken together, these data support the idea that although inhibition of IB, and particularly IKK, blocks cancer-induced wasting, the alternative NF-B signaling pathway is not required. In addition, the downstream NF-B transcription factors do not regulate the transcriptional changes. These data are consistent with the growing body of literature showing that there are NF-B-independent substrates of IKK and IB that regulate physiological processes.
Publication Title
C26 cancer-induced muscle wasting is IKKβ-dependent and NF-kappaB-independent.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone.
Publication Title
Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze.
Publication Title
Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Forkhead BoxO (FoxO) transcription factors expressed in adult skeletal muscle promote muscle atrophy during various catabolic conditions. We have identified the genome wide target genes and biological networks regulated by FoxO in skeletal muscle during Colon-26 (C-26) cancer cachexia.
Publication Title
Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
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GSE59653- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used an Aldefluor assay system to study the signaling pathways that regulate the frequency and maintenance of ALDH-positive cell population in MCF-7 cells as a CSC model.
Publication Title
Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation.
Sample Metadata Fields
Cell line
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