Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor with high mortality rates. Merkel cell polyomavirus (MCPyV), identified in the majority of MCC, may drive tumorigenesis via viral T antigens. However, mechanisms underlying pathogenesis in MCPyV-negative MCC remain poorly understood. To nominate genes contributing to pathogenesis of MCPyV-negative MCC, we performed DNA microarray analysis on 30 MCCs. MCPyV status of MCCs was determined by PCR for viral DNA and RNA. 1593 probe-sets were differentially expressed between MCPyV-negative and -positive MCC, with significant differential expression defined as at least 2-fold change in either direction and p-value of 0.05. MCPyV-negative tumors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response genes. Validation studies included immunohistochemistry demonstration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors. In conclusion, our data suggest that loss of RB1 expression may play an important role in tumorigenesis of MCPyV-negative MCC. Functional and clinical validation studies are needed to determine whether this tumor suppressor pathway represents an avenue for targeted therapy.
Distinct gene expression profiles of viral- and nonviral-associated merkel cell carcinoma revealed by transcriptome analysis.
Specimen part
View SamplesMacrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sex, Age, Specimen part, Treatment, Time
View SamplesMacrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.. The data cast further doubt upon the predictive value of mouse models of inflammatory disease.
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Specimen part, Treatment, Time
View SamplesTo study the effect of balanced chromosomal rearrangements on gene expression, we compared the transcriptomes of cell lines from control and t(11;22)(q23;q11) individuals. This translocation between chromosomes 11 and 22 is the only recurrent constitutional non-Robertsonian translocation in humans. The number of differentially expressed transcripts between the translocated and control cohort is significantly higher than that observed between control samples alone, suggesting that balanced rearrangements have a greater effect on gene expression than normal variation. Altered expression is not limited to genes close to the translocation breakpoint suggesting that a long-range effect is operating. Indeed we show that the nuclear position of the derivative chromosome is altered compared to the normal chromosomes. Our results are consistent with recent studies that indicate a functional role for nuclear position in regulating the expression of some genes in mammalian cells. They may also have implications on reproductive separation, as we show that reciprocal translocations not only provide partial isolation for speciation but also significant changes in transcriptional regulation through alteration of nuclear chromosomes territories.
The effect of translocation-induced nuclear reorganization on gene expression.
Sex, Age, Specimen part
View SamplesHuman myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
No sample metadata fields
View SamplesHuman myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
No sample metadata fields
View SamplesModern functional genomic approaches may help to better understand the molecular events involved in tissue morphogenesis and to identify molecular signatures and pathways. We have recently applied transcriptomic profiling to evidence molecular signatures in the development of the normal chicken chorioallantoic membrane and in tumor engrafted on the CAM. We have now extended our studies by performing a transcriptome analysis in the wound model of the chicken CAM which is another relevant model of tissue morphogenesis. To induce granulation tissue formation, we performed wounding of the chicken CAM and compared gene expression to normal CAM at the same stage of development. Matched control samples from the same individual were used. We observed a total of 282 genes up-regulated and 44 genes downregulated assuming a false-discovery rate at 5 % and a fold change > 2. Furthermore, bioinformatics analysis lead to the identification of several categories that are associated to organismal injury, tissue morphology, cellular movement, inflammatory disease, development and immune system. Endothelial cell data filtering leads to the identification of several new genes with an endothelial cell signature. In summary, the chick chorioallantoic wound model allows the identification of gene signatures involved in granulation tissue formation and neoangiogenesis. This may constitute a fertile ground for further studies.
Gene signatures in wound tissue as evidenced by molecular profiling in the chick embryo model.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Role of TAZ as mediator of Wnt signaling.
Cell line, Treatment
View SamplesTo investigate the role of TAZ downstream of APC and beta-catenin in mammary epithelial cells cells, we compared the expression profiles of MCF10-T1k (MII) cells transfected with siControl, siAPC, siAPC+siTAZ, sibeta-catenin, or sibeta-catenin+siTAZ.
Role of TAZ as mediator of Wnt signaling.
Cell line, Treatment
View SamplesTo investigate the role of TAZ downstream of the abberrant Wnt signaling in CRC cells, we compared the expression profiles of parental SW480 cells (empty vector) transfected with siControl, siTAZ, sibeta-catenin or reconstituted with wild type APC and transfected with siControl
Role of TAZ as mediator of Wnt signaling.
Cell line, Treatment
View Samples