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Bos taurus
9 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Bovine chondrocyte-seeded and mesenchymal stem cell (MSC)-seeded agarose were cultured for 28 days in chemically defined media containing 10 ng/mL TGF-beta3. Chondrogenic differentiated MSCs were compared to chondrocytes at this timepoint and to undifferentiated MSCs harvested at day 0.
Publication Title
Evaluation of the complex transcriptional topography of mesenchymal stem cell chondrogenesis for cartilage tissue engineering.
Sample Metadata Fields
Specimen part, Subject
View Samples- Bos taurus
- 6 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Long-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling).
Publication Title
Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel.
Sample Metadata Fields
Specimen part, Disease
View Samples- Bos taurus
- 12 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
The innate repair and regeneration potential of skeletal tissues such as the intervertebral disc and articular cartilage is extremely limited, in part due to their avascularity and low cell density. Despite recent advances in MSC-based disc and cartilage regeneration, key challenges remain, including the sensitivity of these cells to in vivo microenvironmental stress such as low oxygen and nutrient levels. The objective of this study was to investigate whether preconditioning with hypoxia and/or transforming growth factor-beta (TGF-) can enhance MSC survival and extracellular matrix production in a low oxygen and nutrient-limited microenvironment. Secondarily, the effects of donor variability on the response of MSCs to preconditioning was examined. MSCs from multiple bovine donors were preconditioned in monolayer in normoxia or hypoxia, with or without TGF-.
Publication Title
Hypoxic Preconditioning Enhances Bone Marrow-Derived Mesenchymal Stem Cell Survival in a Low Oxygen and Nutrient-Limited 3D Microenvironment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Endothelial inflammation contributes to the pathogenesis of numerous human diseases; however, the role of tumor endothelial inflammation in the growth of experimental tumors and its influence on the prognosis of human cancers is less understood. TNF-, an important mediator of tumor stromal inflammation, is known to target the tumor vasculature. In this study, we demonstrate that B16-F1 melanomas grew more rapidly in C57BL/6 wild-type (WT) mice than in syngeneic mice with germline deletions of both TNF- receptors (KO). This enhanced tumor growth was associated with increased COX2 inflammatory expression in WT tumor endothelium compared to endothelium in KO mice. We purified endothelial cells from WT and KO tumors and characterized dysregulated gene expression, which ultimately formed the basis of a 6-gene Inflammation-Related Endothelial-derived Gene (IREG) signature. This inflammatory signature expressed in WT tumor endothelial cells was trained in human cancer datasets and predicted a poor clinical outcome in breast cancer, colon cancer, lung cancer and glioma. Consistent with this observation, conditioned media from human endothelial cells treated with pro-inflammatory cytokines (TNF- and interferons) accelerated the growth of human colon and breast tumors in immune-deprived mice as compared with conditioned media from untreated endothelial cells. These findings demonstrate that activation of endothelial inflammatory pathways contributes to tumor growth and progression in diverse human cancers.
Publication Title
Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
Benign prostatic hyperplasia (BPH) is a common urological disease that adversely affects quality of life among elderly males, but its etiology remains poorly understood. We show that the expression of the androgen receptor (AR) is decreased in the luminal epithelial cells of human BPH specimens and is inversely correlated with the degree of regional prostatic inflammation. Overall design: To identify the extracellular signaling that promotes epithelial proliferation, we performed RNA sequencing of FACS-isolated prostate luminal cells from tamoxifen-treated control and K8-AR mice (with knockout of androgen receptor).
Publication Title
Non-Cell-Autonomous Regulation of Prostate Epithelial Homeostasis by Androgen Receptor.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression of the EMT-inducing transcription factor Snail is enhanced in different human cancers. To investigate the in vivo role of Snail during progression of epithelial cancer, we used a mouse model with skin-specific overexpression of Snail. Snail transgenic mice spontaneously developed distinct histological subtypes of skin cancer, such as basal cell carcinoma, squamous cell carcinoma and sebaceous gland carcinoma. Development of sebaceous gland carcinomas strongly correlated with the direct and complete repression of Blimp-1, a central regulator of sebocyte homeostasis. Snail expression in keratinocyte stem cells significantly promotes their proliferation associated with an activated FoxM1 gene expression signature, resulting in a larger pool of Mts24-marked progenitor cells. Furthermore, primary keratinocytes expressing Snail showed increased survival and strong resistance to genotoxic stress. Snail expression in a skin-specific p53-null background resulted in accelerated formation of spontaneous tumours and enhanced metastasis. Our data demonstrate that in vivo expression of Snail results in de novo epithelial carcinogenesis by allowing enhanced survival, expansion of the cancer stem cell pool with accumulated DNA damage, a block in terminal differentiation and increased proliferation rates of tumour-initiating cells.
Publication Title
Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
GSE12771- Homo sapiens
- 242 Downloadable Samples
- Illumina human-6 v1.0 expression beadchip
Description
We generated a blood-derived transcriptional signature that discriminates patients with lung cancer from non-affected smokers. When applied to blood samples from one of the largest prospective population-based cancer studies (the European Prospective Investigation into Cancer and Nutrition), this signature accurately predicted the occurrence of lung cancer in smokers within two years before the onset of clinical symptoms. Such a blood test could be used as a screening tool to enable early diagnosis of lung cancer at a curable stage.
Publication Title
Blood-based gene expression signatures in non-small cell lung cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 62 Downloadable Samples
- NextSeq 500
Description
This study examines the transcriptional changes invoked by activation of gp130 signaling in different mouse models of B cell lymphomagenesis. In order to study the in vivo effects of aberrant activity of IL-6/IL-6R/gp130-JAK/STAT3 signaling, we designed a transgene that allows conditional expression of L-gp130 by generating a ROSA26 knock-in mouse strain where compound L-gp130 and ZsGreen expression from the CAG promoter is prevented by a loxP- and a rox-flanked stop cassette. Total RNA extracted from purified B cells from young CD19Cre+/- ;L-gp130fl/+ and wildtype control mice was sequenced using unique molecular identifiers (UMI) in a paired end design where read1 corresponds to the cDNA and read2 contains the UMI. Furthermore, aging CD19Cre+/- ;L-gp130fl/+ animals developed tumors located predominantly in mesenteric lymph nodes. Infiltration of CD19;L-gp activated B cells was determined by Flow Cytometry and ZsGreen expression. Total RNA from tumors generally containing >60% ZsGreen+ cells was profiled as described above, for tumors with lower CD19;L-gp activated B cell content FACS was applied. In order to study the effects of activated IL-6/IL-6R/gp130-JAK/STAT3 signaling on Eµ-Myc-driven lymphomagenesis, CD19Cre;L-gp130fl;Eµ-Myc triple transgenic mice were generated and fetal liver hematopoietic stem/progenitor cell (FL-HSPC) grafts were transplanted into lethally irradiated syngeneic mice alongside FL-HSPC from CD19Cre;L-gp130f and Eµ-Myc control mice. Lastly, IL-6/IL-6R/gp130-JAK/STAT3 signaling was activated in the entire hematopoetic system using Vav1Cre resulting in Vav1Cre+/- ;L-gp130fl/+ animals. Independent of the time point of activation during hematopoietic and B cell differentiation, all Cre;L-gp compound mice succumbed to tumors of B cell origin. Overall design: Bulk gene expression data are presented for (i) purified B cells from wildtype control mice (n=6) and young CD19;L-gp mice (n=4), (ii) tumors detected in aging CD19;L-gp mice with a mature (n=11) and plasma cell phenotype (n=6), respectively, (iii) tumors arising in lethally irradiated syngeneic mice after transplantation of fetal liver hematopoietic stem/progenitor cells from CD19;L-gp;Myc (n=9), CD19;L-gp (n=7) and Eµ-Myc (n=9) mice, respectively, and (iv) malignant B cells from Vav1;L-gp mice (n=13).
Publication Title
Activated gp130 signaling selectively targets B cell differentiation to induce mature lymphoma and plasmacytoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
In vitro differentiation of embryonic stem cells (ESC) provides models that reproduce in vivo development and cells for therapy. Whether the epigenetic signatures that are crucial for brain development and function and that are sensitive to in vitro culture are similar between native brain tissues and their artificial counterpart generated from ESC is largely unknown. Here, using RNA-seq we have compared the parental origin-dependent expression of imprinted genes (IGs), a model of epigenetic regulation, in cerebral cortex generated either in vivo, or from ESCs using in vitro corticogenesis, a model that reproduces the landmarks of in vivo corticogenesis. For a majority of IGs, the expressed parental alleles were the same for in vivo and in vitro cortex. In most cases, this choice was already set in ESCs and faithfully maintained during the 3 weeks of in vitro corticogenesis. Confirming these findings, methylation, which selects the parental allele to be transcribed, was also largely equivalent between the 2 types of cortex and ESCs. Our results thus indicate that the allele specific expression of imprinted transcripts, a model of epigenetic regulation resulting from a differential methylation of parental genomes, is mostly mimicked in cortical cells derived from ESC. Overall design: We have crossed two strains of mice (B6 and JF1) that display more than 12 million of SNPs (Takada et al., Genome Res. 2013 Aug;23(8):1329-38. doi: 10.1101/gr.156497.113). We have then analyzed allele specific expression transcriptome-wide using RNA-seq on hybrid F1 cortex generated either in vivo or in vitro from ESCs. In addition, we have used 2 different developmental stages of in vivo cortex (E13.5, P0) and three stages in vitro (undiffererentiated ESC, and differentiated into cortex for 12 and 21 days) to measure the dynamics of parental expression. Please note that [1] the same raw data files were used to generate the ''*allele-specific_sense_read_bases_by_gene_withoutContamination.txt'' processed data files. [2] The samples associated with each file are indicated in the file column header (as their GSM accession numbers). [3] The readme.txt file contains the data processing steps, file description.
Publication Title
In Vitro Corticogenesis from Embryonic Stem Cells Recapitulates the In Vivo Epigenetic Control of Imprinted Gene Expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted-resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (~3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were non-recurrent, we observed a number of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2 and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the non-classical regulators of mRNA-processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a significant enrichment of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML.
Publication Title
Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.
Sample Metadata Fields
Specimen part, Disease
View Samples