The effect of a novel form of macrophage colony-stimulating factor (CSF1-Fc) on gene expression in the liver.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Kristin Sauter
PROVIDER: E-GEOD-52636 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The expression was designed to determine whether exposure to CSF1-Fc has any effect on liver-specific gene expression in pigs. livers from pigs exposed to CSF1-Fc
2016-08-01 | E-GEOD-78837 | biostudies-arrayexpress
Project description:The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages Macrophages derived from the C57BL/6 strain of mouse were challenged with increasing doses of LPS over a 24 hour time-course (0.5ng/ml, 5ng/ml, or 50ng/ml LPS). BALB/c derived macrophages were treated with any of 5ng/ml LPS, 10U/ml of recombinant mouse interferon-beta, or 10U/ml interferon-gamma, over a 24 hour timecourse. Sampling times were 0 hours (pre-treatment) and 1, 2, 4, 8, and 24 hours post-treatment in each case. 64 samples in total were analysed. These incorporated 6 different timecourse studies. A combination of statistical filtering using the Empirical Bayes function in Bioconductor package (R statistical software), and co-expression analysis using the network analysis tool BioLayout Express 3D, was used to compare the timecourse studies.
2014-03-24 | E-GEOD-44292 | biostudies-arrayexpress
Project description:Successful derivation of a specific cell lineage from pluripotent stem cells will tremendously facilitate the clinical usage of pluripotent stem derived somatic cells. Herein, we demonstrate that ER71/Etv2, GATA2 and Scl form a core network in hemangioblast development and that transient co-expression of these three factors robustly induced hemangioblasts from ES cells. Such induced hemangioblasts potently generated hematopoietic and endothelial cells in culture as well as in vivo, warranting the evaluation of these cells in the future for repairing and/or regenerating hematopoietic and/or angiogenic defects. We have established a doxycycline inducible ES cell, iEGS, in which ER71/Etv2, GATA2 three transcription factors can be transiently co-expressed by doxycycline induction. We further analyzed the downstream target genes and signaling pathways at 6, 12 and 24hrs after ER71/Etv2, GATA2 induction. These data were obtained from three independent experiments.
2014-02-03 | E-GEOD-45147 | biostudies-arrayexpress
Project description:Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; and Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84. Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, dehydrated airway surface liquid and mucus, and reduced mucus clearance associated with accumulation of mucus plugs/plaques. The data provided here represents mRNA expression data from disseccted whole trachea (distal and proximal ends cut 3-4 cartliage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. PND 0 trachea are histologically normal, a tracheal mucus plug/obstruction develops around PND 3, the plug is receding to more distal airways by PND 10, and the trachea is again histologically normal by PND 42. The data from the WT mice provides a global look at mRNA changes across time, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to mucus obstruction to be queried. The data presented for the purified is part of a larger body of work evaluating gene expression in whole lung, trachea, and purified macrophages. 30 total macrophage samples were analyzed; three from each timepoint (postnatal day 0, 3, 10, and 42) for both wildtype and Scnn1b-transgenic mice grown in specific-pathogen-free facilities and from postnatal day 42 wildtype and Scnn1b-transgenic mice maintained in a germ-free facility. In our manuscript, we were most interested in changes between WT and Scnn1b-Tg mice, however, the data can also be used to evaluate changes in gene expression across time (postnatal day 0, 3, 10, and 42). This data can also be used to evaluate the differences in macrophage biology at postnatal day 42 when mice are grown in specific-pathogen-free versus germ-free environments.
2014-09-11 | E-GEOD-47548 | biostudies-arrayexpress
Project description:Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engrafted in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them. Clec4F+ Kupffer cells were isolated and sorted from livers from adult WT mice or KC-DTR or KC-DTR littermate control mice +/- 50ng DT at indicated timepoints. 19 samples (arrays) in total. RNA was isolated, amplified with Nugene pico kit, converted to cDNA and then hybridised on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.
2015-11-21 | E-GEOD-75225 | biostudies-arrayexpress
Project description:Early diagnosis of transthyretin (TTR) amyloid diseases remains challenging because of variable disease penetrance. Currently, patients must have an amyloid positive tissue biopsy to be eligible for disease modifying therapies. Early diagnosis is often difficult because the patient exhibits apparent symptoms of polyneuropathy or cardiomyopathy, but has a negative amyloid biopsy. Thus, there is a pressing need for more objective, quantitative diagnostics and biomarkers of TTR-aggregation-associated polyneuropathy and cardiomyopathy. This is especially true in the context of clinical trials demonstrating significant disease modifying effects, e.g. when the TTR tetramer stabilizer tafamidis was administered to familial amyloid polyneuropathy (FAP) patients early in the disease course. When asked if the findings of the tafamidis registration trial were âsufficiently robust to provide substantial evidence of efficacy for a surrogate endpoint that is reasonably likely to predict a clinical benefitâ the advisory committee said yes, but the FDA rejected the tetramer stabilization surrogate biomarker required for orphan tafamidis approvalâhence, acceptable biomarkers are badly needed. Herein, we explored whether peripheral blood cell mRNA expression profiles could differentiate symptomatic from asymptomatic V30M FAP patients, and if such a profile would normalize upon tafamidis treatment. We demonstrate that blood cell gene expression patterns reveal sex-independent as well as male and female specific inflammatory signatures in symptomatic FAP patients, but not in asymptomatic carriers, that normalize in FAP patients 6 months after tafamidis treatment. Thus these signatures have potential both as an early diagnostic and as a surrogate biomarker for measuring response to treatment in FAP patients. Study Subjects: Tafamidis-treated and untreated V30M FAP patients, asymptomatic V30M carriers, and healthy, age- and sex-matched controls without TTR mutations had whole blood drawn. RNA was extracted from a total of 309 peripheral blood samples collected in PAXgene tubes (Qiagen). RNA Extraction and Microarray Processing: RNA was extracted with the PAXgene RNA Whole Blood Kit. Each RNA sample (100ng) was amplified and labeled with the Ambion WT Express Kit and hybridized to Affymetrix HuGene 1.1 ST Arrays using the Affymetrix GeneTitan Multi-Channel (MC) platform. Normalized signals were generated using Robust Multichip Average (RMA) in Partek Genomics Suite software version 6.6. Probesets on the DNA microarrays with low expressed signals were determined using a kernel density plot, and signals <Log2 of 6 were excluded from analysis.
2016-08-09 | E-GEOD-67784 | biostudies-arrayexpress
Project description:Df16(A)+/- mice line is a model of human 22q11 microdeletion syndrome. We conducted an unbiased evaluation of the transcriptional difference in the prefrontal cortex between mutant and wild type animals at exon level. These mice were generated by chromosomal engineering and carry a microdeltion of ~1.3Mb in the mouse locus syntenic to the human 22q11.1 The reasoning behind this expression profiling is that consistent alterations in transcriptional programs reflect either downstream (immediate or remote) effects of the deficiency or reactive (compensatory) changes, and can thus point to affected biological processes and molecular functions. Df(16)A+/- mice line is a model of human 22q11 microdeletion syndrome. Adult mutant mice and their wild type littermate were selected. Prefrontal cortex tissues were dissected, total RNA were extracted, processed and hybridized on Affymetrix microarrays. We sought to obtain difference of expression profiles between mutant and wild mice at exon level.
2013-10-21 | E-GEOD-45935 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-24 | E-GEOD-53248 | biostudies-arrayexpress
Project description:Medulloblastoma, the most common malignant pediatric brain tumor, is highly heterogeneous with distinct molecular subtypes and cellular origins. Although current treatments improve survival rates, patients suffer severe treatment-related side effects and often relapse of tumors carrying resistance mutations, underscoring an urgent need for alternative targeted therapies. Currently, the genetic alterations underlying this disease are not fully understood. Here we identify GNAS, encoding the G-protein Gs-alpha, as a potent tumor suppressor gene in medulloblastoma. GNAS specifically defines a subset of aggressive Sonic Hedgehog (Shh)-group medulloblastomas. Gnas loss-of-function in distinct lineage progenitors of the developing hindbrain suffices to initiate medulloblastoma. We find that Gs-alpha is highly enriched at primary cilia of granule neuron precursors and suppresses Shh signaling not only by regulating classic cAMP-dependent pathway but also controlling ciliary trafficking of Smoothened. Concurrent cAMP elevation and Smoothened inhibition robustly arrests tumor cell growth in Gnas mutants. We further reveal oligodendrocyte progenitors as a novel cellular origin for anatomically-distinct Shh-associated medulloblastomas. Together, we identify a previously unrecognized tumor suppressor function of Gs-alpha in medulloblastoma partially mediated through inhibiting Shh signaling, and uncover Gs-alpha as a molecular link across disparate cells of origin among Shh-group medulloblastomas, pointing to G- protein modulation as a potential therapeutic avenue. Transgenic medulloblastoma mouse models were analyzed by Affymetrix Mouse Gene 1.1 ST Array in order to determine their molecular subgroup. Tumors extracted from hGFAP:GnasCKO and Oligo1:GnasCKO transgenic mice were analyzed in 8 replicates each, together with normal mouse cerebellum.
2014-08-24 | E-GEOD-60417 | biostudies-arrayexpress
Project description:Immunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients. A total of 46 PBMC samples representing blood draws from four time points in the first 9 recipients were processed for microarray analysis (The Scripps Research Institute, La Jolla, CA). The analyzed time points were: immediately pre-operatively in the absence of immunosuppression (n=9); post-operatively at 1 year (n=8, range 11-13 months); at 2 years (n=12, range 18-25 months); >3 years (n=17, range 32-48 months). (At year 2 and at > 3 years, repeated samples were obtained from individual subjects, and at one year, one subject had a technically unsatisfactory sample.) To discount the effects of immunosuppression on gene expression, microarray data were included on whole blood from 18 healthy human subjects (controls: GSE40586; NCBI Gene Expression Omnibus [GEO] repository).
2013-04-01 | E-GEOD-45593 | biostudies-arrayexpress