Leptospirosis is a neglected zoonotic disease of global importance. Despite its prevalence, pathogenesis is still poorly understood. Our aim was to discover transcripts responsable for pathogenicity of leptospirosis. We compared the transcriptome profiles of saprophyte, attenuated and virulent strain of Leptospira spp.
Transcriptome datasets of macrophages infected with different strains of <i>Leptospira</i> spp.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The histone chaperone CAF-1 safeguards somatic cell identity.
Specimen part, Time
View SamplesCellular differentiation involves profound changes in the chromatic landscape, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNAi screens targeting chromatin factors during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Remarkably, subunits of the chromatin assembly factor-1 (CAF-1) complex emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Suppression of CAF-1 increased reprogramming efficiency by several orders of magnitude and facilitated iPSC formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 as a novel regulator of somatic cell identity during transcription factor-induced cell fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting.
The histone chaperone CAF-1 safeguards somatic cell identity.
Specimen part, Time
View SamplesTo understand the effect of high and low GA levels on plant metabolism and development in Arabidopsis we made use of the GA biosynthesis inhibitor paclobutrazol (PBZ) and exogenously applied GA. The whole genome response at the translation level was assessed by immunopurification of polysomes from PBZ- and GA treated plants expressing FLAG-tagged ribosomal protein L18 (RPL18B). Polysomal associated RNA was isolated and subjected to affymterix ATH1 CHIP analysis. A total of 140 genes were statistically determined to be differentially translated after GA treatment whereas 89 genes where affected PBZ treatment. Our analysis revealed that GA and PBZ have opposing effects on the expression of cell wall and wax layer biosynthesis related genes. In addition, many genes involved in secondary metabolism are upregulated upon PBZ treatment. A set of SAUR-like genes important for mediating auxin responses are downregulated by PBZ, which is of interest to coordinatian of GA levels with growth and development. Interestingly, GA treatment induces the upregulation of transcription factors related to plant defense and senescence, which is in agreement with the early flowering upon GA treatment. Our study provides a first picture of the response of Arabidopsis to altered GA levels at the translation level, and thus will be valuable for understanding gene regulation at the polysome level.
Translatome and metabolome effects triggered by gibberellins during rosette growth in Arabidopsis.
Specimen part, Treatment
View SamplesACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushings disease (CD)] is the most common cause of endogenous Cushings syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, 10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also identified potential biological pathways associated with growth and invasiveness, TGF- and G protein signaling pathways, DNA damage response pathway, and pathways associated with focal adhesion. Our study revealed a differential pattern of genetic signature in a subgroup of MAC, supporting a genetic influence on corticotrophinomas in patients with CD.
Transcriptome Analysis Showed a Differential Signature between Invasive and Non-invasive Corticotrophinomas.
Sex, Specimen part, Disease
View SamplesTo understand how an inhibition of the mitochondrial ATP synthase affects transcriptional programming and to identify potential candidates of the signaling machinery involved in ATP synthase deficiency responses, we used oligomycin on seedling liquid cultures. Seedlings were harvested at time points 0, 1 and 4 h after the start of oligomycin and control (EtOH) treatments. Already 1 h after addition of oligomycin a total of 102 genes were more than threefold up-regulated and 14 genes were repressed, with most of them showing persistent changes. After 4 h, 580 additional genes were more than threefold up-regulated, and 152 genes were repressed by oligomycin. Several genes for alternative NAD(P)H dehydrogenases and alternative oxidases (AOX1a, AOX1d and NDA1) were up-regulated early, and additional homologs (NDA2, NDB2, NDB4 and AOX1b) followed 4 h after the start of treatment. Several genes for subunits of complex I, complex IV and the ATP synthase were induced whereas hardly any genes encoding enzymes of glycolysis and the TCA cycle changed. Additionally, four of five hallmark genes for oxidative stress were increased by oligomycin. These genes are At2g21640 (UPOX), At1g19020, At1g05340 and At1g57630 and code for proteins of unknown function. Among oxidative stress proteins with known functions, several H2O2-responsive Glutathione-S-transferases and BCS1 (CYTOCHROME BC1 SYNTHESIS) were strongly up-regulated already after 1 h. BCS1 is induced by salicylic acid and independent of other reactive oxygen signaling (ROS) pathways, such as H2O2. The results indicate that several different ROS and defense signaling pathways were induced simultaneously by oligomycin. This is further corroborated by induction of several transcription factors of the WRKY and NAC families, which have been previously implicated in coordinating cellular defense signaling.
Downregulation of the δ-subunit reduces mitochondrial ATP synthase levels, alters respiration, and restricts growth and gametophyte development in Arabidopsis.
Specimen part, Treatment
View SamplesThis study investigated possible molecular changes in the oral mucosa of head and neck squamous cell carcinoma patients submitted to chemoradiotherapy with and without low-level laser therapy by cDNA microarray analysis.
cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study.
Specimen part, Disease, Disease stage
View SamplesBovine leukemia virus (BLV) Tax is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach.
Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis.
Cell line
View SamplesHuman T cell leukemia virus type 1 (HTLV-1) Tax is potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. In this study, a large-scale host cell signaling events related to cellular proliferation were used to identify genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis.
Visualizing spatiotemporal dynamics of apoptosis after G1 arrest by human T cell leukemia virus type 1 Tax and insights into gene expression changes using microarray-based gene expression analysis.
Cell line
View SamplesThere is an association between transcriptome and the exercise-related phenotype. Peripheral blood cells suffer alterations in the gene expression pattern in response to perturbations caused by exercise. The acute response to endurance activates stress and inflammation, as well as growth and tissue repair responses.
PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples