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GSE69082
Homo sapiens
4 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Klotho is critical for the survival of triple negative breast cancer (TNBC) cells HCC1395, since its depletion leads to decreased cell viability, cell cycle arrest and apoptosis.
Publication Title
γKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a low/low/high/low or LLHL, which allowed the identification of genes regulated by mTORC1 by performing the appropriate comparisons
Publication Title
Regulation of TFEB and V-ATPases by mTORC1.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 71 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.
Publication Title
BAP1 loss defines a new class of renal cell carcinoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here that Snail1 plays also a key role in tumor associated fibroblasts since is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-b; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that tumor cells co-transplanted with Snail1 depleted fibroblasts show lower invasion than those xenografted with control fibroblasts. Finally Snail1 depletion in mice prevents the formation of breast tumors and decreased their invasion. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to its effect in EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial cells.
Publication Title
Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis.
Sample Metadata Fields
Specimen part
View Samples- Vitis vinifera
- 14 Downloadable Samples
- Affymetrix Vitis vinifera (Grape) Genome Array (vitisvinifera)
Description
To understand the fruit changes and mechanisms involved in the compatible grapevine-virus interaction, we analyzed the berry transcriptome in two stages of development (veraison and ripening) in the red wine cultivar Cabernet Sauvignon infected with Grapevine leaf-roll-associated virus-3 (GLRaV-3). Analysis of global gene expression patterns indicate incomplete berry maturation in infected berries as compared to uninfected fruit suggesting viral infection interrupts the normal berry maturation process.
Publication Title
Compatible GLRaV-3 viral infections affect berry ripening decreasing sugar accumulation and anthocyanin biosynthesis in Vitis vinifera.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Silicosis, a fibrotic granulomatous lung disease, may occur through accidental high-dose or occupational inhalation of silica, leading to acute/accelerated and chronic silicosis, respectively. While chronic silicosis has a long asymptomatic latency, lung inflammation and apoptosis are hallmarks of acute silicosis. In animal models, histiocytic granulomas develop within days after high-dose intratracheal silica instillation. However, following chronic inhalation of occupationally relevant doses of silica, discrete granulomas resembling human silicosis arise months after the final exposure without significant lung inflammation/apoptosis. To identify molecular events associated with chronic silicosis, lung RNAs from controls or chronically silica-exposed rats were analyzed by Affymetrix at 28 wk after silica exposures. Results suggested a significant upregulation of 144 genes and downregulation of seven genes. The upregulated genes included complement cascade, chemokines/chemokine receptors, G-protein signaling components, metalloproteases, and genes associated with oxidative stress. To examine the kinetics of gene expression relevant to silicosis, qPCR, ELISA, Luminex-bead assays, Western blotting, and/or zymography were performed on lung tissues from 4 d, 28 wk, and intermediate times after chronic silica exposure and compared with 14 d acute silicosis samples. Results indicated that genes regulating fibrosis (secreted phosphoprotein-1, CCL2, and CCL7), redox enzymes (superoxide dismutase-2 and arginase-1), and the enzymatic activities of matrix metalloproteinases 2 and 9 were upregulated in acute and chronic silicosis; however, proinflammatory cytokines were strongly upregulated only in acute silicosis. Thus, inflammatory cytokines are associated with acute but not chronic silicosis; however, genes regulating fibrosis, oxidative stress, and metalloproteases may contribute to both acute and chronic silicosis.
Publication Title
Fibrogenic and redox-related but not proinflammatory genes are upregulated in Lewis rat model of chronic silicosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In rice (Oryza sativa L.), the haplotype at the multigenic SUBMERGENCE 1 (SUB1) locus determines survival of prolonged submergence. SUB1 encodes two or three group VII Ethylene Response Factor (ERF) family transcription factors, SUB1A, SUB1B and SUB1C. A highly submergence-inducible SUB1A allele is present in lines that are submergence tolerant. This gene is the determinant of submergence tolerance. Here, the heterologous ectopic expression of rice SUB1A and SUB1C in Arabidopsis thaliana was employed to assess the transcriptional network mobilized by ectopic expression of SUB1A and SUB1C.
Publication Title
Expression of rice SUB1A and SUB1C transcription factors in Arabidopsis uncovers flowering inhibition as a submergence tolerance mechanism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Illumina HiSeq 2500
Description
Dermal lymphatics form a network that connects all the hair follicles in skin and localize in proximity to the Hair Follicle Stem Cell. RNA sequencing analyses of isolated dermal lymphatics at two different time points of the hair follicle cycle (P55 and P70) indicate the existence of dynamic signaling networks associated with lymphatic remodeling, immune trafficking, and HF signaling. Overall design: Prox1CreERT2; ROSA26-LSL-eYFP mice of P55 (Mid Telogen) and P70 (Late telogen) were sacrificed and eYFP positive cells were isolated from the backskin.
Publication Title
Lymphatic vessels interact dynamically with the hair follicle stem cell niche during skin regeneration in vivo.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
HaCat cell cycle experiment: During the somatic cell cycle, DNA and epigenetic modifications in DNA and histones are copied to daughter cells. DNA replication timing is tightly regulated and linked to GC content, chromatin structure, andgene transcription, but how maintenance of histone modifications relates to replication timing and transcription is less understood.The gene expression patters on HaCaT keratinocytes during the cell cycle is studied by a time series analysis of synchroniced cells sampled at 3 hour intervals. We show that genes enriched with the repressive chromatin mark histone H3 lysine 27 tri-methylation are transcribed during DNA replication . The gene expression is related to replication timing, as genes expressed during G1/S transition andearly S phase generally have higher GC content and are replicated earlier than genes expressed during late S phase. These results indicate widespread replication-dependent expression in mammals and support a role for replication in transiently activating transcription of epigenetically silenced genes.
Publication Title
Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 14 Downloadable Samples
- NextSeq 500
Description
Acute myeloid leukemia (AML) is associated with poor prognosis, and there is a strong need to develop new therapeutic strategies to improve treatments. We performed a cytokine screen with 114 recombinant proteins to identify selective negative regulators of primitive murine AML cells relative to normal bone marrow cells. The top candidate identified was interleukin 4 (IL4), as it showed the most selective inhibition of leukemia cell growth. Stimulating leukemia cells ex vivo with IL4 and transplanting the cells into mice resulted in reduced leukemia burden and prolonged survival compared with controls. In contrast, IL4 did not inhibit the function of normal hematopoietic stem and progenitor cells in long-term bone marrow repopulation assays. Moreover, we found that IL4 treatment of leukemia cells induced Stat6 phosphorylation, and that leukemia cells with Stat6 knocked out using CRISPR/Cas9-genetic engineering were partially resistant to IL4 stimulation, revealing Stat6 as a critical mediator of the IL4 effect. To evaluate whether IL4 has in vivo therapeutic efficacy, we expressed IL4 ectopically in leukemia cells in vivo and also injected IL4 into leukemic mice; both strategies resulted in the suppression of the leukemia cell burden and increased survival. Further analysis revealed that IL4 treatment induces apoptosis in the leukemia cells. Importantly, IL4 exposure also inhibited the growth and survival of primary AML patient cells. In summary, these findings demonstrate that IL4 selectively inhibits AML cells in a Stat6-dependent manner, thus revealing IL4 as a candidate therapeutic agent in AML. IL4 (ProSpec, East Brunswick NJ, USA) was resuspended following the provider guidelines and stored in aliquotes at -80 °C. Mouse MLL-AF9 leukemia cells were provided by Dr. Benjamin Ebert (Brigham and Women’s Hospital, Boston MA, USA). The murine leukemia cells were cultured in SFEM (StemCell Tech) supplemented with 1% penicillin/streptomycin at 37 °C with 5% CO2. Overall design: Mouse MLL-AF9 leukemia cells were grown in 20 ng/mL IL3 with or without IL4 (100 ng/mL) for 18 hours.
Publication Title
Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner.
Sample Metadata Fields
Specimen part, Subject
View Samples