Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4+CD25highFoxp3+ T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation.
Comparative transcriptional and phenotypic peripheral blood analysis of kidney recipients under cyclosporin A or sirolimus monotherapy.
Specimen part, Disease
View SamplesWe report the RNAseq data obtained from 50.000-100.000 CD31-/CD45- pneumocytes isolated by FACS from mice harboring a normal dose or one extra copy of the Sirt1 gene, and a tamoxifen-inducible oncogenic KI alelle of KRasG12V after 4 weeks of tamoxifen treatment. Pneumocytes with the activated form of the inducible KRasG12V oncogene sere selected making use of the reporter gene LacZ (located next to the oncogene in the same polycistronic mRNA), by loading CD31-/CD45- pneumocytes with the LacZ-activated fuorogenic molecule FDG prior to FACS sorting. Overall design: Four replicates of each genetic group (Sirt1-WT and Sirt1-Tg) pneumocytes were used for this study. Sirt1-WT were used as reference controls.
Sirt1 protects from K-Ras-driven lung carcinogenesis.
Subject
View SamplesWe report the RNAseq data obtained from 50.000-100.000 CD31-/CD45- pneumocytes isolated by FACS from mice harboring a normal dose or one extra copy of the Sirt1 gene, and a tamoxifen-inducible oncogenic KI alelle of KRasG12V after 4 weeks of tamoxifen treatment plus 2 weeks without tamoxifen. Pneumocytes with the activated form of the inducible KRasG12V oncogene sere selected making use of the fluorescent reporter gene Katushka (located at an independent locus), by detecting Katushka fluorescence. Overall design: Four replicates of each genetic group (Sirt1-WT and Sirt1-Tg) pneumocytes were used for this study. Sirt1-WT were used as reference controls.
Sirt1 protects from K-Ras-driven lung carcinogenesis.
Sex, Subject
View SamplesBackground: Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM.
Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas.
Specimen part, Disease
View SamplesMechanical forces are essential for normal fetal lung development. However, the cellular and molecular mechanisms regulating this process remain largely unknown. In the present study, we used oligonucleotide microarray technology to investigate gene expression profile in cultured E19 rat fetal lung type II epithelial cells exposed to a level of mechanical strain similar to that observed in utero. Significance Analysis of Microarrays (SAM) identified 92 genes differentially expressed by strain. Interestingly, several members of the solute carrier family of amino acid transporters, genes involved in amino acid synthesis and development, and amiloride-sensitive epithelial sodium channel gene were induced by strain. These results were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Thus, this study identifies genes induced by strain that may be important for amino acid signaling pathways, protein synthesis and development in fetal type II cells. In addition, these data suggest that mechanical forces may contribute to facilitate lung fluid reabsorption in preparation for birth. Taken together, the present investigation provides further insights into how mechanical forces may modulate fetal lung development.
DNA microarray reveals novel genes induced by mechanical forces in fetal lung type II epithelial cells.
Sex, Specimen part
View SamplesCNIs drastically modify the Treg specific transcriptional program in vivo in an IL-2 dependent manner
IL-2 therapy restores regulatory T-cell dysfunction induced by calcineurin inhibitors.
Specimen part, Treatment
View SamplesVariant FhlA133 (Q11H, L14V, Y177F, K245R, M288K, and I342F) had eight- fold higher hydrogen production than FhlA wild-type under 30 min of anaerobic incubation in modified-complex 20 mM formate at 37C. The mechanism by which the FhlA133 mutations increase hydrogen production is by increasing the transcription of all of the genes activated by the native FhlA (FHL complex).
Protein engineering of the transcriptional activator FhlA To enhance hydrogen production in Escherichia coli.
No sample metadata fields
View SamplesA number of studies find that metastasis suppressor proteins, including RhoGDI2, may function in part though controlling expression of genes regulating metastasis (reviewed in Smith and Theodorescu, Nature Reviews Cancer, 2009, PMID: 19242414). To uncover systematically gene expression patterns dependent on RhoGDI2 expression, we profiled gene expression in stably transfected control (GFP empty vector) UM-UC-3 bladder carcinoma cells (which have lost endogenous expression of RhoGDI2, as occurs commonly in the progression of bladder cancer PMID: 15173088), as well as stably transfected GFP-tagged RhoGDI2 expressing UM-UC-3 cells.
RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration.
Specimen part, Cell line
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of primary mouse embryonic palatal mesenchymal (MEPM) cells from wild type mice as well as those with a neural crest specific conditional inactivation of the Tgfbr2 gene. The latter mice provide a model of cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions.
Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice.
Specimen part
View SamplesThis in-vitro study suggests the inflammatory environment of naive epithelial cells can induce epigenetic modulation of innate immune responses at the level of histone methylation and potentially lead to long-term impacts on anti-viral immunity.
IFN-γ Influences Epithelial Antiviral Responses via Histone Methylation of the RIG-I Promoter.
Cell line, Treatment
View Samples