Conjunctival samples from 60 individuals with and without the clinical signs of active trachoma were analysed on the U133 Plus 2.0 arrays. Global transcriptional changes characteristic of disease and infection phenotypes were identified. Two analysis methods found large numbers of differentially regulated genes and the existence of networks of co-expressed genes. There were signatures characteristic of the host defence response with evidence supporting infiltration of various types of leukocytes and activation of innate responses of epithelial cells. Two separate methods could classify disease and infection phenotype based on transcription signatures with 70% accuracy. These results provide an insight into the complexity of the acute response in trachoma but are able to partly explain the biology of trachoma through the identification of pathways and gene expression sets useful to future studies on chlamydial immunopathogenesis.
Human conjunctival transcriptome analysis reveals the prominence of innate defense in Chlamydia trachomatis infection.
Sex, Age, Specimen part, Disease, Race
View SamplesPurpose: Cellular senescence is a cell stress response resulting in permanent growth arrest and the production of an altered pro-inflammatory secretory profile known as the senescecnce-associated secretory phenotype (SASP). The induction of senescence in astrocytes, a cell type responsible for maintaining homeostasis within the central nervous system (CNS) and responding to CNS insults, has been implicated in neurodegenerative disease. However, little is known about the senescent transcriptome in CNS-derived cell types including astrocytes. Methods: To better understand senescence-associated gene expression changes in astrocytes, we investigated global changes in the astrocyte transcriptome using RNA-seq following the induction of oxidative stress-induced senescence with hydrogen peroxide. Results: During senescence, we find evidence of a loss of brain expressed transcripts involved in diverse CNS processes including neuronal differentiation and development, gliogenesis, axonogenesis, and learning and memory as well as a loss of transcripts involved in MHC class II antigen processing and presentation. In addition, we find evidence for induction of the senescent phenotype including a loss of transcripts involved in cell division and an increase in the mRNA level of inflammatory mediators suggestive of a SASP. Conclusions: Overall, our findings suggest a loss of differentiated function in senescent astrocytes and a gain in neuroinflammatory function as part of the SASP as a potential mechanisms for dysfunction in the aging brain. Overall design: Examination of transcriptome changes by RNAseq in pre-senescent and senescent astrocytes using 2 biological replicates per condition
Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence.
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View SamplesDuring senescence of detached rice leaves, tryptophan (Trp) and Trp-derived secondary metabolites such as serotonin and 4-coumaroylserotonin accumulated in concert with methanol (MeOH) production. This senescence-induced MeOH induction was closely associated with levels of pectin methylesterase (PME)1 mRNA and PME enzyme activity. Exogenous challenge of detached rice leaves with 1% MeOH accelerated Trp and serotonin biosynthesis with induction of the corresponding genes. No other solvents including ethanol resulted in a Trp-inducing effect. This MeOH-induced Trp synthesis was positively regulated by abscisic acid but negatively regulated by cytokinin, suggesting hormonal involvement on the action of MeOH. Endogenous overproduction or suppression of MeOH either by PME1 overexpression or RNAi gene silencing revealed that PME1 overexpressing lines produced twofold higher Trp levels with elevated Trp biosynthetic gene expression, whereas RNAi lines showed twofold reduction in Trp level in healthy control rice leaves, suggesting that MeOH acts as an endogenous elicitor to enhance Trp biosynthesis. Among many transcription factors induced following MeOH treatment, the WRKY family showed significant induction patterns of which WRKY14 appeared to play a key regulatory role in MeOH-induced Trp and Trp-derived secondary metabolite biosynthesis.
Methanol is an endogenous elicitor molecule for the synthesis of tryptophan and tryptophan-derived secondary metabolites upon senescence of detached rice leaves.
Specimen part
View SamplesSSEA1+ c-kit+cells sorted from mouse embryonic stem cells differentiated for 4 days in 10uM Retinoic acid do not form teratomas when transplated into SCID mice while Pten-/- cells do.
Loss of Pten causes tumor initiation following differentiation of murine pluripotent stem cells due to failed repression of Nanog.
Specimen part
View SamplesAPC inactivation is the early process in the tumorigenesis of colorectal cancer. We established organoid cultures from intestines of genetically modifeid mice harboring Apcfl/fl, Tacc3wt/wt or Apcfl/fl, Tacc3fl/fll and R26CreERT2 allele
Suppression of intestinal tumors by targeting the mitotic spindle of intestinal stem cells.
Specimen part
View SamplesTranscription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access have not been well known in mammalian cells. We show a physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed conditions, and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads preloading of RNA polymerase II and opens chromatin structure by recruiting a histone chaperone FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanistic basis for constitutive HSF1 access to nucleosomal DNA, which is important for both basal and inducible gene expression.
RPA assists HSF1 access to nucleosomal DNA by recruiting histone chaperone FACT.
Specimen part
View SamplesIn addition to transcriptional regulation, mRNA degradation critically contributes to gene expression as shown by various biological analysis. The CCR4-NOT complex serves as a major deadenylase that initiates mRNA degradation.
CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins.
Specimen part, Time
View SamplesDefects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of electron transport chain component, cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage dependent growth and acquired invasive phenotypes. Disruption of CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling, includes activation of PI3-kinase, IGF1R and Akt, Ca2+ sensitive transcription factors and also, TGF1, MMP16, periostin that are involved in oncogenic progression. Whole genome expression analysis showed up regulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mtDNA depletion, though distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in CcO complex can potentially induce tumor progression.
Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming.
Cell line
View SamplesWe used microarrays to select the genes associated glioma patients survival.
Gene expression signature-based prognostic risk score in patients with glioblastoma.
Sex, Age, Disease, Disease stage
View SamplesWe report gene expression data for FACS sorted zebrafish mpeg1:mCherry + and mpx:EGFP + cells collected from whole embryos at 72 hours post fertilization (hpf). We also report gene expression data for the remaining, transgene negative, portion of these embryos. Overall design: ~1,000 mpeg1:mCherry+; mpx:EGFP+ transgenic embryos were homogenized, filtered, and sorted using FACS into PBS, collecting >50,000 cells for each of the three populations: mpeg1:mCherry+, mpx:EGFP+ and double negative (no double positive cells were collected as there was almost no overlap between mCherry and EGFP expression).
Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization.
No sample metadata fields
View Samples