ABSTRACT: This SuperSeries is composed of the following subset Series: GSE36816: GY118F downstream targets in iPS cells GSE36817: GY118F downstream effect in EpiSCs Refer to individual Series
Project description:This microarray was performed to gain insight in the effect of GY118F stimulation in EpiSCs. This array is part of the following paper to be published in Nature Communications: “JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naïve pluripotency” by Anouk L. van Oosten, Yael Costa, Austin Smith & José C.R. Silva Gy0 a, gy0 b, gy0 c (triplicate samples for GY118F EpiSCs in N2B27+Activin+Fgf) c0 a, c0 b, c0 c (triplicate samples for Control EpiSCs in N2B27+Activin+Fgf) gy3 b, gy3 c (duplicate samples for GY118F EpiSCs in N2B27+Activin+Fgf stimulated with GCSF for 3 hours) c3 a, c3 b, c3 c (triplicate samples for Control EpiSCs in N2B27+Activin+Fgf stimulated with GCSF for 3 hours) Within the manucript genes of interest were defined as those that were significantly upregulated (P<0.01) above a 1.4 fold change threshold in GCSF stimulated GY118F EpiSCs as compared to those not stimulated, but for which the expression did not significantly change upon GCSF stimulation in the control. The fold change in expression was calculated by 2^absolute value of subtracted normalised data.
Project description:This microarray was performed to gain insight in the downstream targets of GY118F in iPS cells. This array is part of the following paper to be published in Nature Communications: “JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naïve pluripotency” by Anouk L. van Oosten, Yael Costa, Austin Smith & José C.R. Silva The samples analysed were: - GY118F iPS cells derived and maintained in N2B27 plus GCSF (t0, indicated in data as nlng t0 a), -same cells but from which GCSF was withdrawn for 12 or 24 hours (t-12, t-24, indicated in data as nlng t-12 a and nlng t-24 a) -and cells to which after withdrawal for 12 or 24 hours, subsequently GCSF was added back for 2 hours and 40 minutes (t-12+2h40m, t-24+2h40m, indicated in data as nlng t-12+2.4 a and nlng t-24+2.4 a). To obtain the data as presented in the manuscript the following was done:The values obtained for t0 were subtracted from t-12 and t-24. The values for t-12 and t-24 were subtracted from t-12+2h40m and t-24+th40m respectively. Subsequently the data was devided into genes that appeared to go down upon withdrawal of GCSF and up upon readdition and those with the converse gene expression pattern. Then a threshold of ?1.4 fold change was applied. If a certain gene obeyed these criteria for all described comparisons, the gene was considered a potential downstream target. The fold change in expression was calculated by 2^absolute value of subtracted normalised data.
Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 65 unique diagnostic biopsy specimens were profiled. Samples with paired surgical resection specimens (not included in this submission) are denoted in the Sample 'characteristics' field.
Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 26 unique pairs of biopsy and surgical resection specimens were profiled. Paired samples are denoted in the Sample 'characteristics' field.
Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 37 unique diagnostic biopsy specimens were profiled. Samples with paired surgical resection specimens (not included in this submission) are denoted in the Sample 'characteristics' field.
Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 5 unique pairs of diagnostic biopsy and surgical resection specimens were profiled. Paired samples are denoted in the Sample 'characteristics' field.
Project description:Gene expression profiling of primary stromal cell cultures isolated from human endometrium and ovarian endometriosis. Samples are derived from the endometrium of 6 healthy patients and the endometriomas of 6 diseased patients. The results indicate the gene expression differences between these two cell populations. Stromal cells were obtained from human normal endometrial tissues and ovarian endometriomas. The tissues were digested enzymatically, and pure stromal cell populations were established.
Project description:Bile acid (BA) homeostasis is maintained through a feedback loop operated by the nuclear hormone receptors FXR and SHP. Here we show that contrary to the current models placing FXR upstream of SHP in a linear regulatory pathway, the phenotypic consequence of the combined loss of both receptors is much more severe than the relatively modest impact of the loss of either Fxr or Shp alone. This is highlighted by the dramatic elevation of hepatic and serum BA levels in the double knockout (DKO) mice as early as three weeks of age coupled with a commensurate increase in Cyp7A1 expression and alterations in BA homeostatic genes. In addition, we find several genes necessary for C21 steroid biosynthetic pathway as novel targets for FXR and SHP. The elevated BAs result in severe hepato-pathology but the DKO mice surprisingly do not develop complete liver failure and live for over a year. Their survival is accompanied by an adaptive proliferation of the resident liver progenitor cell population, known as oval cells. Overall, these data demonstrate that FXR and SHP function coordinately to maintain BA homeostasis, and identify DKO mice as a novel genetic model for juvenile cholestatic disorders and for oval cell activation. Liver samples collected from FXR-/-, SHP-/-, and FXR-/-/SHP-/- animals at 3 or 5 weeks were hybridized to Illumina mouse REF-8 v1.1 arrays in duplicate.
Project description:Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent form of hepatic disease and feeding mice a High-Fat, High-Caloric (HFHC) diet is a standard model of NAFLD. In order to better understand the genetic basis of NAFLD, we conducted an expression quantitative trait locus (eQTL) analysis of mice fed a HFHC diet. 265 (A/J × C57BL/6J) F2 male mice were fed a HFHC diet for 8 weeks. QTL analysis was utilized to identify genomic regions that regulate hepatic gene expression of Xbp1s and Socs3. We identified two overlapping loci for Xbp1 and Socs3 on Chr 1 (164.0-185.4 Mb and 174.4-190.5 Mb, respectively) and Chr 11 (41.1-73.1 Mb and 44.0-68.6 Mb, respectively), and an additional locus for Socs3 on Chr 12 (109.9-117.4 Mb). C57BL/6J-Chr 11A/J/ NaJ mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3 gene expression (p<0.05), while C57BL/6J-Chr 1A/J/ NaJ mice retained the C57BL/6 phenotype. In addition, we replicated the eQTLs on Chr 1 and 12 (LOD scores ? 3.5) using mice from the BXD murine reference panel challenged with CCl4 to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs for Xbp1 and Socs3 on Chr 1 and 11, and consomic mice confirmed that replacing the C57BL/6 with the A/J Chr 11 resulted in an A/J phenotype for Xbp1 and Socs3 gene expression. Identification of the genes for these eQTLs will lead to a better understanding of the genetic factors responsible for NAFLD and potentially other hepatic diseases. Liver samples from eight-week-old AJ and C57BL6J males fed a High Fat High Calorie diet.