Modern 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 study is to identify downstream targets of homeobox gene CDX1. The study assayed the expression of 2 pairs of stably transfected colorectal cancer cell lines: The CDX1 nonexpressing CRC cell line HCT116 was stably transfected with either CDX1 cDNA in the pRC/CMV expression vector (HCT116-CDX1) or with vector control (HCT116-Vec). The CDX1-expressing CRC cell line LS174T was similarly transfected with either a pSilencer vector containing a short sequence of CDX1 siRNA (LS174T-siRNA) , or a pSilencer vector containing a scrambled siRNA sequence as a control (LS174T-Vec).
Gastrointestinal differentiation marker Cytokeratin 20 is regulated by homeobox gene CDX1.
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View SamplesFormation of blood vessels requires the concerted regulation of an unknown number of genes in a spatial-, time- and dosage-dependent manner. We investigated vascular development in vivo by determining global gene regulation throughout the formation of the chick chorio-allantoic membrane (CAM). Our study provides a comprehensive molecular map of vascular maturation during developmental angiogenesis and might thus be a valuable resource to streamline further research of candidates susceptible to mediate pathological angiogenesis.
Correlating global gene regulation to angiogenesis in the developing chick extra-embryonic vascular system.
No sample metadata fields
View SamplesHuman pancreatic adenocarcinoma cells were grafted on the chick chorioallantoic membrane (CAM). Human and chicken GeneChips were used simultaneously to study gene regulation during PDAC cell invasion.
Netrin-1 mediates early events in pancreatic adenocarcinoma progression, acting on tumor and endothelial cells.
No sample metadata fields
View SamplesWe determined gene expression profiles which were induced in the chick chorio-allantoic membrane 24 h after application of recombinant human VEGF.
Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
No sample metadata fields
View SamplesConstitutive low level DNA damage in RNASEH2 deficiency is linked to innate immune activation. Hierarchical clustering of over 16000 transcripts revealed remarkably similar profiles in patients with lupus erythematosus and patients with AGS with up-regulation of genes involved in DNA damage signaling and type I-IFN signaling. Overall design: Comparison of transcriptional profiles of native RNASEH2-deficient patient fibroblasts with wild type cells.
Defective removal of ribonucleotides from DNA promotes systemic autoimmunity.
No sample metadata fields
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 SamplesWe have analyzed the transcript expression in different LCM-dissected cell layers isolated from mouse retinas adapted to light or dark in order to identify transcripts potentially targetted by retinal microRNAs which are regulated in response to light treatment
Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs.
Specimen part, Treatment
View SamplesThe cytosolic protein Sharpin is as a component of the linear ubiquitin chain assembly complex (LUBAC), which regulates NF-B signaling in response to specific ligands. Its inactivating mutation in Cpdm (chronic proliferative dermatitis mutation) mice causes multi-organ inflammation, yet this phenotype is not transferable into wildtype mice by hematopoietic stem cell transfer. Recent evidence demonstrated that Cpdm mice additionally display low bone mass, but the cellular and molecular causes of this phenotype remained to be established. Here we have applied non-decalcified histology together with cellular and dynamic histomorphometry to perform a thorough skeletal phenotyping of Cpdm mice. We show that Cpdm mice display trabecular and cortical osteopenia, solely explained by impaired bone formation, whereas osteoclastogenesis is unaffected. We additionally found that Cpdm mice display a severe disturbance of articular cartilage integrity in the absence of joint inflammation, supporting the concept that Sharpin-deficiency affects mesenchymal cell differentiation. Consistently, Cpdm mesenchymal cells displayed reduced osteogenic capacitiy ex vivo, yet this defect was not associated with impaired NF-B signaling. A molecular comparison of wildtype and Cpdm bone marrow cell populations further revealed that Cpdm mesenchymal cells produce higher levels of Cxcl5 and lower levels of IL1ra. Collectively, our data demonstrate that skeletal defects of Cpdm mice are not caused by chronic inflammation, but that Sharpin is as a critical regulator of mesenchymal cell differentiation and gene expression. They additionally provide an alternative molecular explanation for the inflammatory phenotype of Cpdm mice and the absence of disease transfer by hematopoetic stem cell transplantation.
Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells.
Specimen part
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