The distinction between primary and secondary ovarian tumors may be challenging for pathologists.
A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer.
Specimen part, Disease stage
View SamplesWe compare the genetic profiles of the primary tumors of uveal melanoma or metastasis to their corresponding xenografts that have been passaged over time.
Patient-derived xenografts recapitulate molecular features of human uveal melanomas.
Disease
View SamplesA high percentage of uveal melanoma patients develop metastatic tumors that predominately occur in the liver. To identify genes associated with metastasis in this pathology, we studied 63 molecular profiles derived from gene expression microarrays performed from enuceated primary tumors.
High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients.
Sex, Age, Specimen part
View SamplesWhile the hypothalamo-pituitary-adrenal axis (HPA) activates a general stress response by increasing glucocorticoid (Gc) synthesis, biological stress resulting from infections triggers the inflammatory response through production of cytokines. The pituitary gland integrates some of these signals by responding to the pro-inflammatory cytokines IL6 and LIF and to a negative Gc feedback loop. The present work used whole-genome approaches to define the LIF/STAT3 regulatory network and to delineate cross-talk between this pathway and Gc action. Genome-wide ChIP-chip identified 3 449 STAT3 binding sites, whereas 2 396 genes regulated by LIF and/or Gc were found by expression profiling. Surprisingly, LIF on its own changed expression of only 85 genes but the joint action of LIF and Gc potentiated the expression of more than a thousand genes. Accordingly, activation of both LIF and Gc pathways also potentiated STAT3 and GR recruitment to many STAT3 targets. Our analyses revealed an unexpected gene cluster that requires both stimuli for delayed activation: 83% of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response.
Regulatory network analyses reveal genome-wide potentiation of LIF signaling by glucocorticoids and define an innate cell defense response.
Specimen part, Time
View Samples[Hela cells]: We performed cdr2 knockdown with a pool of 4 cdr2-specific siRNAs to test whether cdr2 may regulate c-myc target genes as cells passage through mitosis.
The onconeural antigen cdr2 is a novel APC/C target that acts in mitosis to regulate c-myc target genes in mammalian tumor cells.
Cell line
View SamplesThe objective of the present investigation was to utilize the GeneChip Porcine Genome Array from Affymetrix possessing 20, 201 unique probe sets to identify differentially expressed genes during rapid trophoblastic elongation and attachment to the uterine surface in the pig. Identification and characterization of conceptus gene expression patterns during rapid trophoblastic elongation and attachment in the pig will provide a better understanding of the events required for successful implantation and embryonic survival.
Identification of differential gene expression during porcine conceptus rapid trophoblastic elongation and attachment to uterine luminal epithelium.
No sample metadata fields
View SamplesThe paired-end next-generation sequencing of all small RNAs of less than 200 nucleotides in length from four different human cell lines (SKOV3ip1, MCF-7, BJ-Tielf, INOF) allowed us to determine the exact sequence(s) and variations of human box C/D snoRNAs (small nucleolar RNAs), revealing processing patterns of this class of molecules. Two distinct groups of box C/D snoRNAs were identified based on the position of their ends with respect to their characteristic boxes and the terminal base pairing potential. Short box C/D snoRNAs start sharply 4 or 5 nucleotides upstream of their box C and end 2 or 3 nucleotides downstream of their box D. In contrast, long box C/D snoRNAs start 5 or 6 nucleotides upstream of their box C and end 4 or 5 nucleotides downstream of their box D, increasing the likelihood of formation of a k-turn between their boxes C and D. Sequencing of SKOV3ip1 cells following the depletions of NOP58, a core box C/D snoRNA-binding protein and of RBFOX2, a splicing factor, shows that the short box C/D snoRNA forms are significantly more affected by the depletion of RBFOX2 while the long snoRNA forms, which display more canonical box C/D snoRNA features, are significantly more affected by the depletion of NOP58. Together the data suggest that box C/D snoRNAs are divided into at least two groups of RNA with distinct maturation and functional preferences. Overall design: Small RNAs (<200 nucleotides) were isolated from different human cell lines that were either untreated or depleted of NOP58 or RBFOX2 using specific siRNAs. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq.
Simultaneous sequencing of coding and noncoding RNA reveals a human transcriptome dominated by a small number of highly expressed noncoding genes.
No sample metadata fields
View SamplesTranscriptional profiling coupled with blood metabolite analyses were used to identify porcine genes and pathways that respond to a fasting treatment or to a D298N missense mutation in the melanocortin-4 receptor (MC4R) gene. Gilts (12 homozygous for D298 and 12 homozygous for N298) were either fed ad libitum or fasted for 3 days. Fasting decreased body weight and backfat and increased serum concentrations of non-esterified fatty acid and urea. In response to fasting, 7,029 genes in fat and 1,831 genes in liver were differentially expressed (DE, q value less than 0.05). MC4R genotype did not affect gene expression, body weight, backfat depth, and any measured serum metabolite concentration. Pathway analyses of fasting-induced DE genes indicated that both liver and fat down-regulated energetically costly processes such as lipid and steroid synthesis and up-regulated efficient energy utilization pathways. Fasting increased expression of genes in involved in glucose sparing pathways in liver and extracellular matrix pathways in adipose tissue. Within the DE genes, transcription factors (TF) that regulate many DE genes were identified, confirming the involvement of TF that are known to regulate fasting response and implicating additional TF that are not known to be involved in energy homeostatic responses. Interestingly, estrogen receptor 1 transcriptionally controls fasting induced genes in fat that are involved in cell matrix morphogenesis. Our findings indicate a transcriptional response to fasting in two key metabolic tissues of pigs that was corroborated by changes in blood metabolites; and involvement of novel putative transcriptional regulators in the immediate adaptive response to fasting.
Microarray gene expression profiles of fasting induced changes in liver and adipose tissues of pigs expressing the melanocortin-4 receptor D298N variant.
No sample metadata fields
View SamplesResidual feed intake (RFI) is a measure of feed efficiency, where low RFI denotes high feed efficiency. Caloric restriction (CR) is associated with feed efficiency in livestock species and to human health benefits such as longevity and cancer prevention. We have developed pig lines that differ in RFI and are interested to identify the genes and pathways that underlie feed efficiency. Prepubertal Yorkshire gilts with low RFI (n=10) or high RFI (n=10) were fed ad libitum or at 80% of maintenance for eight days. We measured serum metabolites and generated transcriptional profiles of liver and subcutaneous adipose tissue. 6,114 genes in fat and 305 genes in liver were differentially expressed (DE) in response to CR and 311 in fat and 147 in liver were DE due to RFI differences. Pathway analyses of CR-induced DE genes indicated a switch to a conservation mode of energy by down-regulating lipogenesis and steroidogenesis in both liver and fat. Interestingly, CR in pigs altered expression of genes in immune and cell cycle/apoptotic pathways in fat, which may explain part of the CR-driven lifespan enhancement. In-silico analysis of transcription factors revealed ESR1 as a putative regulator of the adaptive response to CR and several targets of ESR1 in our DE fat genes were annotated as cell cycle/apoptosis genes. Lipid metabolic pathway was overrepresented by down-regulated genes due to both CR and low RFI. We propose a common energy conservation mechanism, which may be controlled by PPARA, PPARG, and/or CREB in both CR and feed efficient pigs.
Gene expression profiling of the short-term adaptive response to acute caloric restriction in liver and adipose tissues of pigs differing in feed efficiency.
Age, Specimen part
View SamplesIn this report, Tompkins et al describe the derivation, differentiation stage-specific purification, and genome-wide analysis of cardiomyocytes derived from hESCs. Key features of the molecular programs that define human cardiac muscle cell differentiation were described and researchers observed that cells may harbor epigenetic DNA methylation “memories” that reflect the gene activation history of important developmental genes. Overall design: For RNA-seq. Cardiomyocyte differentiation from human embryonic stem cells (H7). 11 time point pilot time series. D3 and D4 samples FACS sorted for primitive and cardiac mesoderm isolation, respectively. Data from negatives sorts (minus) included as well.
Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation "Memories".
No sample metadata fields
View Samples