Interleukin (IL)-17 plays an important and protective role in host defence and has been demonstrated to orchestrate airway inflammation by cooperating with and inducing proinflammatory cytokines. Mircoarrays were used to identify immediate-early/ primary response IL-17A-dependent gene transcripts in primary human bronchial ASM cells from mild asthmatic and healthy individuals.
IL-17A mediates a selective gene expression profile in asthmatic human airway smooth muscle cells.
Sex, Age, Specimen part, Treatment, Subject, Time
View SamplesMouse ES cells were differentiated for 6 days. Undifferentiated cells (d0) were compared to cells harvested at 24 hour timepoints (d1-d6).
Transcriptional profiling of mouse and human ES cells identifies SLAIN1, a novel stem cell gene.
Age, Specimen part, Cell line, Time
View SamplesUndifferentiated cells of different passage numbers (p19 and p128) were compared to cells differentiated in hanging drops for 5 days (d5 embryoid bodies) or expanded on gelatin coated dishes for a further 9 days (d14 embryoid bodies).
Transcriptional profiling of mouse and human ES cells identifies SLAIN1, a novel stem cell gene.
Age, Specimen part, Cell line, Time
View SamplesHuman tumours show a high level of clonal heterogeneity that contributes to malignant progression and metastasis, but the processes that influence the timing of metastatic dissemination of subclones are unknown. Here, we have used whole exome sequencing of 98 matched benign, malignant, and metastatic skin tumours from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumour, but then evolve separately, acquiring an additional set of mutations during growth at distant sites. Shared mutations between primary carcinomas and their matched metastases have the distinct A>T signature of the initiating carcinogen Dimethylbanzanthracene (DMBA), but non-shared mutations are primarily G>T or C>T substitutions, associated with oxidative stress. We found recurrent point mutations in several hundred genes, including several in the Ras (Hras, Kras, and Pik3ca) pathway. We propose that carcinogen-driven mouse tumour models can aid our understanding of the forces that shape clonal and genetic evolution of human cancers.
Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers.
Sex
View SamplesGene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as signaling pathways including Sonic Hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.
Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.
Sex, Age, Specimen part, Treatment
View SamplesGene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as signaling pathways including Sonic Hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.
Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.
Sex, Specimen part
View SamplesGene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as signaling pathways including Sonic Hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.
Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.
Sex
View SamplesHair follicles are self-renewing organs within the skin which cycle through periods of growth and destruction, with an intervening period of outward quiescence. The hair follicle cycle is driven by Hedgehog and Wnt signaling and affects epithelial thickness, melanin production, immune function, and tumor susceptibility. We have previously shown that somatic alterations to the genome affect the genetic architecture of the skin. This study examines how the hair follicle cycle affects gene the genetic architecture in vivo by genomic and genetic analysis of 343 genetically heterogeneous mice during the hair follicle growth phase (anagen) and quiescent phase (telogen). We use eQTL analysis and differential correlation to identify changes in metabolic and stem cell activity not detected by differential expression. Germline influence in gene expression is profoundly higher during anagen, but this increase is not a simple factor of higher levels of gene expression. The most strongly induced eQTLs were involved in cellular energy metabolism and melanogenesis rather than hair follicle growth or hedgehog signaling. We demonstrate that hair follicle and circadian rhythm pathways are sexually dimorphic, but do not find evidence for an effect of sex on eQTL networks. We also use eQTL gene network analysis to identify candidate causal relationships between expression of genes in the hair follicle and melanin pathways, identifying Mcoln3 as a candidate for the familial melanoma locus on 1p22. To lower the bioinformatic barriers to eQTL network analysis we produced CARMEN, a free open-source stand-alone software package. This study demonstrates how to perform a systems genetic analysis of a heterogeneous tissue studied in vivo under physiologically relevant growth signals.
Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.
Sex, Age, Specimen part
View SamplesGene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as signaling pathways including Sonic Hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.
Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation.
Cell line, Treatment
View Samples