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SRP273032
Homo sapiens
18 Downloadable Samples
Illumina HiSeq 2500
Description
A deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) leads to chronic lung disease. However, the molecular mechanisms are not well understood and therapies that can help all patients remain elusive. CF is associated with abnormalities in fatty acids, ceramides and cholesterol, therefore we examined the impact of CFTR deficiency on lipid metabolism and pro-inflammatory signaling in airway epithelium using mass spectrometric, protein array and RNAseq analyses. We observed a striking imbalance in fatty acid and ceramide metabolism, associated with chronic oxidative stress under basal conditions in CF mouse lung and well differentiated bronchial epithelial cell cultures of CFTR knock out pig and CF patients. Cell autonomous features of all three CF models included high ratios of ω-6- to ω-3-polyunsaturated fatty acids and long- to very long- chain ceramide species (LCC/VLCC). The anti-oxidants glutathione (GSH) and deferoxamine partially corrected the lipid profile indicating that oxidative stress may promote the lipid abnormalities. CFTR-targeted modulators reduced the lipid imbalance and apparent oxidative stress, confirming the CFTR dependence of lipid ratios. RNA sequencing and protein array analysis revealed higher expression and shedding of cytokines and growth factors from CF epithelial cells compared to non-CF cells, consistent with sterile inflammation and tissue remodeling under basal conditions. Treatment with antioxidants or CFTR modulators that mimic the approved combination therapies, Orkambi and Trikafta, did not suppress the inflammatory phenotype. These results suggest that anti-inflammatory therapies may provide additional benefit for CF patients taking CFTR modulator drugs. Overall design: Here we report analysis of nine samples, three of Cf patient (BCF000174), homozygous for F508del CFTR, compared to two non-CF in triplicate each (P21, P11, ErasmusMC, Rotterdam, compared pairwise)
Publication Title
CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Uremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Publication Title
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Several functions have been suggested for the interferon induced transmembrane protein 1 (Iftitm1) gene in mammals. Originally it was identified as a member of a gene family that is highly inducible by type I and type II inteferons. Based on its expression during primordial germ CELl (PGC) specification it was suggested to be required for normal PGC migration. Ifitm1 targeted knockdown experiments in mouse embryos provided evidence that the gene might be necessary for normal somitogenesis. Finally, the complete deletion of the Ifitm gene cluster on mouse chromosome 7 revealed that the five deleted Ifitm1 genes are not essential for PCG migration and fertility. Here, we generated a novel targeted knockin allele of the Ifitm1 gene by replacing its coding region with a lacZ reporter gene to systematically reassess the suggested functions of this gene.
Publication Title
In vivo functional requirement of the mouse Ifitm1 gene for germ cell development, interferon mediated immune response and somitogenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Sus scrofa
- 13 Downloadable Samples
- Porcine Gene 1.0 ST Array (porgene10st)
Description
Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked dystrophin (DMD) gene. The absence of dystrophin protein leads to progressive muscle weakness and wasting, disability and death. To establish a tailored large animal model of DMD, we deleted DMD exon 52 in male pig cells by gene targeting and generated offspring by nuclear transfer. DMD pigs exhibit absence of dystrophin in skeletal muscles, increased serum creatine kinase levels, progressive dystrophic changes of skeletal muscles, impaired mobility, muscle weakness, and a maximum life span of 3 months due to respiratory impairment. To address the accelerated development of muscular dystrophy in DMD pigs as compared to human patients, we performed a genome-wide transcriptome study of M. biceps femoris samples from 2-day-old and 3-month-old DMD and age-matched wild-type pigs. The transcriptome changes in 3-month-old DMD pigs were in good accordance with the findings of gene expression profiles in human DMD, reflecting the processes of degeneration, regeneration, inflammation, fibrosis, and impaired metabolic activity. The transcriptome profile of 2-day-old DMD pigs pointed towards increased protein and DNA catabolism, reduced extracellular matrix formation and cell proliferation and showed similarities with transcriptome changes induced by exercise injury in muscle. Our transcriptome studies provide new insights into congenital changes associated with dystrophin deficiency and secondary complications arising during postnatal development. Thus the DMD pig is a useful model to determine the hierarchy of physiological derangements in dystrophin-deficient muscle.
Publication Title
Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Patients with Klinefelter Syndrome have the karyotype 47,XXY. These men are suffering from hypergonadotropic hypogonadism and are infertile. It is debated whether the different hormonal constitution observed in these patients or different gene expression
Publication Title
Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Expression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.
Publication Title
A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in 3 normal testes.
Publication Title
Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Conrad et al. Nature 456, 344349 (2008) have generated human adult germline stem cells (haGSCs) from human testicular tissue, which they claim have similar pluripotent properties to human embryonic stem cells (hESCs). Here we investigate the pluripotency of haGSCs by using global gene-expression analysis based on their gene array data and comparing the expression of pluripotency marker genes in haGSCs and hESCs, and in haGSCs and human fibroblast samples derived from different laboratories, including our own. We find that haGSCs and fibroblasts have a similar gene-expression profile, but that haGSCs and hESCs do not. The pluripotency of Conrad and colleagues haGSCs is therefore called into question.
Publication Title
Human adult germline stem cells in question.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Knockdown of HCLS1 mRNA in CD34+ hematopoietic cells resulted in a severe diminished in vitro myeloid differentiation which was in line with downregulation of a set of genes, e.g., of Wnt or PI3K/Akt signaling cascades. We performed microarrays to evaluate specific genes and signaling systems regulated by HCLS1 in hematopoietic cells.
Publication Title
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Rattus norvegicus
- 21 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Rats were given pulmonary embolism by i.v. injection of 25 micron polystyrene microspheres or 0.01% Tween20 solution as vehicle control
Publication Title
Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples