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GSE27174
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Lineage-specific transcription factors, which drive cellular identity during embryogenesis, have been shown to convert cell fate when express ectopically in heterologous cells. Herein, we screened the key molecular factors governing the dopaminergic neuronal specification during brain development for their ability to generate similar neurons directly from mouse and human fibroblasts. Remarkably, we found a minimal set of three factors Mash1, Nurr1 and Lmx1a/b able to elicit such cellular reprogramming. Molecular and transcriptome studies showed reprogrammed DA neurons to faithfully recapitulate gene expression of their brain homolog cells while lacking expression of other catecholaminergic neuronal types. Induced neurons showed spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain DA neurons. The three factors were able to elicit DA neuronal conversion in human fibroblasts from prenatal or adult fibroblasts of healthy donors and a Parkinsons disease patient. Generation of DA induced neurons from somatic cells might have significant implications in studies of neural development, disease in vitro modeling and cell replacement therapies.
Publication Title
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Fibrotic diseases are a group of pathologies with high incidence and mortality. Despite extensive research efforts, efficient therapies are still not available. Understanding the molecular mechanisms driving the onset, progression and possible resolution of fibrosis is a prerequisite to the development of successful therapies. The central role of the TGF-beta pathway and myofibroblasts in the pathogenesis of fibrosis is now generally accepted. The possible mechanisms of myofibroblast elimination or dedifferentiation, on the other hand, are still almost uncharted territory. Basic fibroblast growth factor (bFGF) is able to suppress myofibroblastic differentiation of mesenchymal cells, but the underlying mechanism has not been studied in detail. Here, we show that sustained expression of the transcription factor EGR4, which is inducible by bFGF, in primary chicken embryo dermal myofibroblasts results in suppression of the myofibroblastic phenotype, characterized by the loss of smooth muscle actin fibers and a substantial reduction in the production of extracellular matrix. Detailed analysis of the possible molecular mechanisms revealed FOXG1, BAMBI, NAB1, NAB2 and DUSP5 genes forming an EGR4 regulated network counteracting autocrine TGF-beta signaling.
Publication Title
Effective myofibroblast dedifferentiation by concomitant inhibition of TGF-β signaling and perturbation of MAPK signaling.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Myofibroblast is a specific type of mesenchymal cell characterized by synthesis of extracellular matrix and contractile activity. While it serves a beneficial function during tissue wound healing under physiological conditions, it can cause devastating damage to organs afflicted with fibrosis. Myofibroblasts are also present in tumor stroma and contribute actively to tumor growth and spreading. Chicken embryo dermal myofibroblasts (CEDM) represent a novel ex vivo model suitable for the analysis of myofibroblastic phenotype as they show strongly pronounced, uniform and self-sustained myofibroblastic phenotype that is stable in time. As myofibroblastic differentiation is controlled chiefly by TGF-beta signaling, the understanding of the differentiation program entails the determination of TGF-beta-regulated genes. To achieve such a goal, we performed oligonucleotide microarray analysis of CEDM cells treated with a selective TGFBR1 kinase inhibitor. Genes reported previously to be under the control of TGF-beta signaling in mammalian cells appeared among the affected genes also in CEDM cells and many so far unknown TGF-beta targets were revealed.
Publication Title
Molecular analysis of the TGF-beta controlled gene expression program in chicken embryo dermal myofibroblasts.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human airway epithelial cells cultured in vitro at air-liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, and produces mucin, and are widely used as a model of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed global gene expression correlated well between ALI cells and brushed cells, but there were some differences. Gene expression patterns mirrored differences in proportions of cell types (ALI have higher percentages of basal cells, brushed cells have higher percentages of ciliated cells), with ALI cells expressing higher levels of basal cell-related genes and brushed cells expressing higher levels of cilia-related genes. Pathway analysis showed ALI cells had increased expression of cell cycle and proliferation genes, while brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells are a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences in the in vitro vs in vivo environments need to be considered.
Publication Title
Do airway epithelium air-liquid cultures represent the in vivo airway epithelium transcriptome?
Sample Metadata Fields
Sex, Age
View Samples- Gallus gallus
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
A model of tumor metastasis based on v-src transformed immortalized cell lines was developed. The model consists of highly metastatic PR9692 cell line and a derived clone PR9692-E9 which has lost the metastatic abilities. Introduction of exogenous EGR1 gene into the non-metastasizing PR9692-E9 cells completely restores the metastatic potential. Revealed changes in gene expression provide insight into the molecular mechanisms contolling metastatic behavior of sarcoma cells.
Publication Title
The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to compare gene expression between three HRAS-wild type lines (13, 162d, 165d) and three HRAS-G12S mutant lines (7, 8, 16).
Publication Title
Dysregulation of astrocyte extracellular signaling in Costello syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
While most novel tuberculosis (TB) vaccines are designed for delivery via the muscle or skin for enhanced protection in the lung, it has remained poorly understood whether systemic vaccine-induced memory T cells can readily home to the lung mucosa prior to and shortly after pathogen exposure. We have investigated this issue by using a model of parenteral TB immunization and intravascular immunostaining. We find that systemically induced memory T cells are restricted to the blood vessels in the lung, unable to populate either the lung parenchymal tissue or the airway under homeostatic conditions. We further find that after pulmonary TB infection, it still takes many days before such T cells can enter the lung parenchymal tissue and airway. We have identified the acquisition of CXCR3 expression by circulating T cells to be critical for their entry to these lung mucosal compartments. Our findings offer new insights into mucosal T cell biology and have important implications in vaccine strategies against pulmonary TB and other intracellular infections in the lung.
Publication Title
CXCR3 Signaling Is Required for Restricted Homing of Parenteral Tuberculosis Vaccine-Induced T Cells to Both the Lung Parenchyma and Airway.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. A Nugent scoring system serves as a proxy for determining the ratio of lactobacilli to other vaginal inhabitants where a high score usually represents a diseased state, whilst an intermediate score represents a warning zone. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate score, the effect of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 on the microbiota and host response. The probiotic treatment did not result in changes to clinical parameters such as dryness, irritation and comfort, compared to when placebo was applied. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the proportional abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response and multiplex cytokine analysis showed up-regulation of IL-5. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle trigger molecular changes induced by the host to instillation of probiotic strains.
Publication Title
A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Innate immune memory is a new important area of research. However, innate immune memory at the major mucosal sites remains poorly understood. Here we show that respiratory viral infection induces long-lasting memory alveolar macrophages (AM). Memory AM are programed to express high MHC II, carry a defense-ready gene signature, and produce, upon re-stimulation, neutrophil chemokines. Using a multitude of approaches, we reveal that the priming, but not maintenance, of memory AM requires the help from effector CD8 T cells. T cells jump-start this process in AM via IFN- production. We further find that formation/maintenance of memory AM are independent of monocytes or bone marrow progenitors. Finally, we demonstrate that memory AM are poised for robust trained immunity against bacterial infection in the lung via rapid induction of chemokines and neutrophilia. Our study thus establishes a new paradigm of immunological memory formation whereby adaptive T-lymphocytes render innate memory of mucosal-associated macrophages.
Publication Title
Induction of Autonomous Memory Alveolar Macrophages Requires T Cell Help and Is Critical to Trained Immunity.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Purpose: The goals of this study are to identify the transcriptional profile of retinal ganglion cells (RGCs) with the capacity to regenerate an axon, and contrast this profile with the profile of RGCs that cannot regenerate an axon. Methods: See sample pages for protocols for tissue preparation, RNA extraction and purification, library construction and data processing. Results: RNA from the 12 samples was sequenced to an average depth of 42 million reads. Genes were considered expressed if a gene had an expression of 1 count per million in 3 of the 12 samples. There were 13,406 genes that met this criterion. Conclusions: Our study represents the first analysis by NGS of highly-purified RGCs in the context of axonal injury Overall design: RGC mRNA profiles of melanopsin RGCs and ON-OFF Direction Selective Ganglion Cells (ooDSGCs) were generated by deep sequencing in triplicate, using Illumina HiSeq 2500.
Publication Title
Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples