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Xenopus laevis
4 Downloadable Samples
Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Depolarization of resting membrane potential in select cells in Xenopus larvae induces striking hyperpigmentation due to dysregulation of melanocytes. Here, we show that this non-cell-autonomous process is mediated by cAMP, CREB, and the transcription factors Sox10 and Slug. Our microarray analysis reveals specific transcripts responsive to Vmem levels within a few hours of depolarization, and a set of 517 transcripts whose expression remains altered during the full hyperpigmented phenotype over a week later, linking instructor cell-depolarization to a range of developmental processes and disease states. We also show that voltage-dependent conversion of melanocytes involves the MSH-secreting melanotrope cells of the pituitary, and formulate a model for the molecular pathway linking the bioelectric properties of melanocyte cells microenvironment in vivo to the genetic and cellular changes induced in this melanoma-like phenotype. Remarkably, the phenotype is all-or-none: each individual animal either undergoes melanocyte conversion or not, as a whole. This group decision is stochastic, resulting in varying percentages of hyperpigmented individuals for a given experimental treatment. To understand the stochasticity and dynamic properties of this complex signaling system, we developed a novel computational method that automates the reverse-engineering of stochastic dynamic signaling models. We used this method to discover a network model that quantitatively explained our complex dataset, and even made correct predictions for new experiments that we validated in vivo. Taken together, these data (1) reveal new molecular details about a novel trigger of metastatic-like developmental cell behavior in vivo, (2) suggest new targets for biomedical intervention, and (3) demonstrate proof-of-principle of a computational method for understanding stochastic decision-making by cells during embryonic development and metastasis.
Publication Title
Serotonergic regulation of melanocyte conversion: A bioelectrically regulated network for stochastic all-or-none hyperpigmentation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 80 Downloadable Samples
Illumina HiSeq 2000
Description
The multiple claims about reactivation of the embryonic stem cell (ESC) pluripotency factor OCT4 in somatic cells are highly controversial due to the fact that there is no direct evidence that OCT4 has a functional role in cells other than ESCs. Herein we demonstrate that smooth muscle cell (SMC)-specific knockout of Oct4 within atherosclerotic mice resulted in increased lesion size and multiple changes consistent with decreased plaque stability. SMC-lineage tracing studies showed that lesions from SMC-specific conditional Oct4 KO mice had a reduced number of SMCs likely due to impaired SMC migration. RNA-seq analysis of lesion specimens showed that loss of Oct4 in SMCs was associated with marked activation of genes associated with inflammation and suppression of genes associated with cell migration, a number of which were shown to be activated in cultured SMCs by the combination of hypoxia and oxidized phospholipids in an OCT4-dependent manner. Activation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4 promoter and was HIF1a- and KLF4-dependent. Results provide the first genetic evidence that OCT4 plays a functional role in somatic cells and highlight the importance of further investigation of possible OCT4 functions in somatic cells. Overall design: In vivo: mRNA profiles of 18 week fed Western diet wild type (WT) and Oct4-/- mice were generated by deep sequencing, four animals per group, using Illumina HiSeq 2000. In vitro: a smooth muscle cell wild type (WT) and Oct4-/- (KO) primary aortic cell line was generated and used. mRNA profiles were generated by deep sequencing, in triplicates, using Illumina HiSeq 2000, for the following groups: WT-normoxia-vehicle; WT-normoxia-POVPC; KO-normoxia-vehicle; KO-normoxia-POVP; WT-hypoxia-vehicle; WT-hypoxia-POVPC; KO-hypoxia-vehicle; and KO-hypoxia-POVPC.
Publication Title
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples
GSE5799- Staphylococcus aureus
- 12 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
A triclosan-ciprofloxacin cross-resistant mutant strain of Staphylococcus aureus displays an alteration in the expression of several cell membrane structural and functional genes.
Publication Title
A triclosan-ciprofloxacin cross-resistant mutant strain of Staphylococcus aureus displays an alteration in the expression of several cell membrane structural and functional genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-B but blocked that with RXR, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXR target genes. A dysregulated Acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders.
Publication Title
A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Respiratory innate immunity requires alveolar macrophages, which are specifically targeted by the S. aureus toxin alpha toxin. These data compare the response of alveolar macrophages to S. aureus with or without alpha toxin neutralization.
Publication Title
S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Macaca mulatta
- 108 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. In this study we specifically interrogated the transcriptional signatures of animals treated with FR104 monotherapy and FR104/Sirolimus combination therapy
Publication Title
Combined OX40L and mTOR blockade controls effector T cell activation while preserving T<sub>reg</sub> reconstitution after transplant.
Sample Metadata Fields
Specimen part, Subject
View Samples- Macaca mulatta
- 100 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. In this study we specifically interrogated the transcriptional signatures of animals treated with KY1005 monotherapy and KY1005/Sirolimus combination therapy
Publication Title
Combined OX40L and mTOR blockade controls effector T cell activation while preserving T<sub>reg</sub> reconstitution after transplant.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta, Homo sapiens
- 105 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Sample Metadata Fields
Specimen part, Subject
View Samples- Macaca mulatta
- 81 Downloadable Samples
Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. This transcriptome analysis enables an unsupervised approach to the identification of targets for disease control using a model with an immune system that closely overlaps with the human and has a high degree of cross-reactivity with human antibody-based therapeutics.
Publication Title
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD (GSE73723). Within these profiles we discovered potentially druggable targets not previously implicated in GVHD, prominently including aurora kinase A (AURKA). In this study, we performed a planned comparison of AURKA gene expression in HCT-recipients with clinical GVHD and compared it to expression in HCT-recipients without clinical GVHD.
Publication Title
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Sample Metadata Fields
Specimen part, Subject
View Samples