HSF1 is a major transcriptional regulator of heat shock responses. Many cells activate HSF1 in response to heat shock temperatures (>42oC) and other cellular stress causing agents. Unlike other cell types, T cells activate HSF1 in response to T cell activation or when exposed to febrile (40oC) temperatures, suggesting a role for HSF1 beyond the heat-shock response.
Heat shock transcription factor 1 is activated as a consequence of lymphocyte activation and regulates a major proteostasis network in T cells critical for cell division during stress.
Specimen part, Treatment
View SamplesGene expression data from VHL teratomas comparing genes differentially expressed based on apoptotic response to tumor microenvironment.
Pleiotropic effects of the trichloroethylene-associated P81S VHL mutation on metabolism, apoptosis, and ATM-mediated DNA damage response.
Specimen part
View SamplesPurpose: We investigated the tetrachloroethylene associated changes in kidney transcriptomes among healthy mice, nonalcoholic fatty liver disease mice, and nonalcoholic steatohepatitis mice. Overall design: Male C57BL/6J mice were fed a low-fat diet (4% fat), high-fat diet (31% fat), or methionine/choline/folate deficient diet. Following an 8-week diet, mice were administered either a single dose of tetrachloroethylene (PERC, 300 mg/kg/d in 5% Alkamuls-EL620 in saline, 5 mL/kg) and euthanized at 24 hours post dose, or five consecutive daily doses of PERC or vehicle (n=8/diet/treatment) and euthanized at 4hours post dose. The harvested kidneys were subjected to mRNA sequencing using Illumina Hiseq 2500. Jac-NASH-063 was excluded from analysis because it did not have a good yield.
Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice.
Cell line, Treatment, Subject
View SamplesWe report the effect of NAFLD on liver gene expression changes that could impact tetrachloroethhylene metabolism Methods: We fed male C57Bl/6J mice a base diet (BD), high fat (HFD), or methionine/choline/folate deficient high fat diet (MCD) for 8 weeks and then treated them with vehicle or tetrachloroethylene (PERC, 300 mg/kg ig). We only report "basal" differences herein (aka vehicle-treated). Results: We report that there were diet-specific differences in xenobiotic metabolizing genes, and that these genes may be responsible for NAFLD-induced disruption in PERC metabolism Overall design: Examination of liver left lobe gene expression for 3 different diets fed to C57Bl/6J male mice
Impact of Nonalcoholic Fatty Liver Disease on Toxicokinetics of Tetrachloroethylene in Mice.
Sex, Cell line, Treatment, Subject
View SamplesOral squamous cell carcinoma (OSCC) is a lethal disease and early death usually occurs as a result of local invasion and regional lymph node metastases. We used microarrays to identify down or upregulated genes in OSCCs compared with non-malignant controls.
Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation.
Disease, Disease stage, Cell line
View SamplesInfertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.
The epidermal growth factor receptor critically regulates endometrial function during early pregnancy.
Specimen part
View SamplesTo uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors.
Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK.
Sex, Specimen part
View SamplesWe report the application of Illumina small RNA sequencing to normal human skin, as well as uninvolved and involved psoriatic skin. By obtaining over 600 million qualified reads from 20 healthy controls and 47 psoriasis biopsies (uninvolved/involved), we have generated a complete small RNA profile in normal and diseased human skin, with particular emphasis on miRNAs. We report the discovery of 284 putative novel miRNAs as well as 98 differentially expressed miRNAs in psoriatic skin. Overall design: miRNA discovery and expression profiling in 67 normal and psoriatic human skin biopsies
Deep sequencing of small RNAs from human skin reveals major alterations in the psoriasis miRNAome.
Specimen part, Disease, Disease stage, Subject
View SamplesMononuclear cells were isolated from the sternal bone marrow and prepared for multiparametric flow cytometry using an optimized and validated protocol. B-cell subsets of PreBI, PreBII, Immature, Naive, Memory and Plasma cells were isolated and a al of 38 gene expression profiles were generated using the HuEx-1_0-st-v2-micro array chip from Affymetrix to characterize the gene expression in the individual subpopulations.
Long Noncoding RNA Expression during Human B-Cell Development.
Specimen part, Subject
View SamplesLong noncoding RNAs (lncRNAs) have emerged as important regulators of diverse cellular processes, but their roles in the developing immune system are poorly understood. In this study, we analysed lncRNA expression during human B-cell development by array-based expression profiling of eleven distinct flow-sorted B-cell subsets, comprising pre-B1, pre-B2, immature, naive, memory, and plasma cells from bone marrow biopsies (n=7), and naive, centroblast, centrocyte, memory, and plasmablast cells from tonsil tissue samples (n=6), respectively. A remapping strategy was used to assign the array probes to 37630 gene-level probe sets, reflecting the most recent updates in genomic and transcriptomic databases, which enabled expression profiling of 19579 long noncoding RNAs, comprising 3947 antisense RNAs, 5277 lincRNAs, 7625 pseudogenes, and 2730 additional lncRNAs. As a first step towards inferring the functions of the identified lncRNAs in developing B-cells, we analysed their co-expression with well-characterized protein-coding genes, a method known as guilt by association. By using weighted gene co-expression network analysis, we identified 272 lincRNAs, 471 antisense RNAs, 376 pseudogene RNAs, and 64 lncRNAs within seven sub-networks associated with distinct stages of B-cell development, such as early B-cell development, B-cell proliferation, affinity maturation of antibody, and terminal differentiation. These data provide an important resource for future studies on the functions of lncRNAs in development of the adaptive immune response, and the pathogenesis of B-cell malignancies that originate from distinct B-cell subpopulations.
Long Noncoding RNA Expression during Human B-Cell Development.
Specimen part, Subject
View Samples