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SRP055753
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2500
Description
Cancer originates as the progressive accumulation of genetic mutations in proto-oncogenes and tumor suppressors. However, the early events underlying tumor initiation remain largely elusive, mostly due to the general lack of information regarding the cells-of-origin responsible for tumor formation as well as the precise impacts of genetic insults on tumor initiation in vivo. Here, we demonstrate that Sox2-positive (Sox2+) adult stem cells are responsible for epithelial squamous tumor formation. Conditional expression of oncogenic Kras (KrasG12D) and knockout of p53 (also known as Trp53) in Sox2+ cells quickly and specifically resulted in the formation of squamous tumors in the forestomach and esophagus. GFP-based lineage tracing experiments demonstrated that Sox2+ cells are the cells-of-origin of squamous tumors in the esophagus and forestomach. Of note, our data showed that p53 deletion alone did not suffice for tumor initiation. On the contrary, tumor initiation was observed upon KrasG12D activation whereas p53 deletion further contributed to the malignancy of the generated tumors, pointing out distinct roles for Kras activation and p53 deletion in squamous tumor formation and progression, to which a multihit carcinogenesis model can be applied. Global gene expression analysis revealed secreting factors upregulated in the generated tumors induced by oncogenic Kras, which contribute to tumor progression. Taken together, these results demonstrate that epithelial squamous tumors can specifically originate as a consequence of defined genetic mutations in a Sox2+ cell population and highlight the connections between proliferative stem cells and tumor development in vivo. Overall design: Expression profiling of mouse tissues with genetically induced tumors by RNA-Seq
Publication Title
Mutations in foregut SOX2<sup>+</sup> cells induce efficient proliferation via CXCR2 pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 24 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We show that infant trauma, as modeled by infant paired odor-shock conditioning, results in later life depressive-like behavior that can be modulated by learned infant cues (i.e., odor previously paired with shock). We have previously shown that this infant attachment odor learning paradigm results in the creation of a new artificial maternal odor that is able to control pup behavior and retain its value throughout development. Here, we assess the mechanism by which this artificial maternal odor is able to rescue depressive-like behavior and show that this anti-depressant like effect results in glucocorticoid and serotonin (5-HT) related changes in amygdala gene expression and is dependent on amygdala 5-HT. Furthermore, increasing amygdala 5-HT and blocking corticosterone (CORT) in the absence of odor mimics the adult rescue effects elicited by the artificial maternal odor, suggesting a mechanism by which odor presentation exerts its repair effects.
Publication Title
Enduring good memories of infant trauma: rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 4 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Quorum sensing controls the expression of multiple virulence factors. PA14 genes lasR and rhlR are necessary for quorum sensing via homoserine lactones.
Publication Title
Quorum sensing enhancement of the stress response promotes resistance to quorum quenching and prevents social cheating.
Sample Metadata Fields
Treatment
View Samples- Sus scrofa
- 26 Downloadable Samples
- Illumina HiSeq 2000
Description
Identification of genes and causal mutations regulating growth and fatness traits in pig. Overall design: Transcriptome sequencing of 10 liver samples of two groups of divergent pigs for growth and fatness.
Publication Title
Using RNA-Seq SNP data to reveal potential causal mutations related to pig production traits and RNA editing.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The efficiency of central nervous system (CNS) remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study we show that expression of genes involved in the retinoid X receptor (RXR) pathway are decreased with aging in myelin-phagocytosing cells. Loss of RXR function in young macrophages mimics aging by delaying remyelination after experimentally-induced demyelination, while RXR agonists partially restore myelin debris phagocytosis in aged macrophages. The FDA-approved RXR agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in aging human monocytes to a more youthful profile. These results reveal the RXR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.
Publication Title
Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
The identification of Atg16L1 as a susceptibility gene has implicated antibacterial autophagy in the pathogenesis of Crohn''s disease, a major type of inflammatory bowel disease (IBD). However, the role of Atg16L1 during extracellular bacterial infections of the intestine has not been sufficiently examined and compared to the function of other IBD susceptibility genes such as Nod2. We now find that Atg16L1 mutant mice are extraordinarily resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. We further demonstrate that Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, and that Atg16L1/Nod2 double mutant mice lose this advantage. These results reveal an unappreciated immuno-suppressive function of an IBD gene, and raise the possibility that gene variants that affect the autophagy pathway were evolutionarily maintained to protect against certain life-threatening infections. Overall design: Twenty samples have been analyzed. All are colonic tissue from mice. Controls are uninfected WT mice, uninfected Atg16L1 mutant mice (Atg16L1HM) (n=3/genotype). Treatment conditions are tissue from WT and Atg16L1 mutant mice 6 days after C. rodentium infection (n=4/genotype) and 15 days after infection (n=3/genotype).
Publication Title
A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
We used microarrays to compare gene expression profile of spleen CD8 T cells from IL-17RA KO and WT mice at different time-point after T. cruzi infection.
Publication Title
IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During <i>Trypanosoma cruzi</i> Infection.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The change in gene expression on the 8th day of gestation was investigated using DNA microarrays.
Publication Title
Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The change in gene expression on the 8th day of gestation was investigated using DNA microarrays. Uterine gene expression of interimplanted sites was analyzed in female mice.
Publication Title
Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples