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SRP044373
Homo sapiens
59 Downloadable Samples
IlluminaHiSeq2000, IlluminaMiSeq
Description
Establishment and application of RNAseq based transcriptome analayis on an archivaed bladder cancer cohort. Overall design: Total RNA profilling 61 archived bladder cancer samples and comparison of 4 pairs of fresh frozen and FFPE bladder cancer samples.
Publication Title
Next-generation RNA sequencing of archival formalin-fixed paraffin-embedded urothelial bladder cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase paralleling the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b-/- mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. Atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohns disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b-/- mice. Taken together, these results provide additional evidence on the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that Atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency
Publication Title
ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Ion Torrent Proton
Description
Objective: Alcoholic hepatitis (AH) is characterized by the expansion of ductular reaction (DR) cells and expression of liver progenitor cell (LPC) markers. The aim of this study was to identify the gene expression profile and associated genes of DR cells and to evaluate its weight in alcoholic disease progression. Design: KRT7+, KRT7- and total liver fractions were laser microdissected from liver biopsies (n=6) of patients with AH and whole transcriptome was sequenced. Gene signature was assessed in transcriptomic data from 41 patients with alcoholic liver disease. Pro-inflammatory profile was evaluated in tissue and serum samples and in human LPC organoids. Results: Transcriptome analysis of KRT7+ DR cells uncovered intrinsic gene pathways of DR and allowed identifying genes associated with DR expressed in AH. In addition, DR gene signature and associated genes correlated with disease progression and poor outcome in AH patients. Importantly, DR presented a pro-inflammatory profile with expression of CXC and CCL chemokines and was associated with infiltrating neutrophils. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators. In vitro, human LPC organoids mimicked ductular reaction gene expression profile and produced chemokines. Moreover, LPC promoted neutrophil migration and enhanced their inflammatory profile. Conclusions: Here we report for the first time the gene expression signature of DR in AH and its association with disease progression. Functional and experimental analysis demonstrates that DR cells have a pro-inflammatory profile, and suggest their involvement in neutrophil recruitment and liver inflammatory response.
Publication Title
Ductular Reaction Cells Display an Inflammatory Profile and Recruit Neutrophils in Alcoholic Hepatitis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Cell line, Treatment, Race
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Objective: Alcoholic hepatitis (AH) is characterized by the expansion of ductular reaction (DR) cells and expression of liver progenitor cell (LPC) markers. The aim of this study was to identify the gene expression profile and associated genes of DR cells and to evaluate its weight in alcoholic disease progression. Design: KRT7+, KRT7- and total liver fractions were laser microdissected from liver biopsies (n=6) of patients with AH and whole transcriptome was sequenced. Gene signature was assessed in transcriptomic data from 41 patients with alcoholic liver disease. Pro-inflammatory profile was evaluated in tissue and serum samples and in human LPC organoids. Results: Transcriptome analysis of KRT7+ DR cells uncovered intrinsic gene pathways of DR and allowed identifying genes associated with DR expressed in AH. In addition, DR gene signature and associated genes correlated with disease progression and poor outcome in AH patients. Importantly, DR presented a pro-inflammatory profile with expression of CXC and CCL chemokines and was associated with infiltrating neutrophils. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators. In vitro, human LPC organoids mimicked ductular reaction gene expression profile and produced chemokines. Moreover, LPC promoted neutrophil migration and enhanced their inflammatory profile. Conclusions: Here we report for the first time the gene expression signature of DR in AH and its association with disease progression. Functional and experimental analysis demonstrates that DR cells have a pro-inflammatory profile, and suggest their involvement in neutrophil recruitment and liver inflammatory response.
Publication Title
Ductular Reaction Cells Display an Inflammatory Profile and Recruit Neutrophils in Alcoholic Hepatitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs.
Publication Title
Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied and -untied toxicity mechanisms common to neurodegenerative diseases.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinsons disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. To gain a better understanding of the consequences of excessive SNCA expression on basal ganglia function, we performed transcriptome analysis of striatal tissue from male Thy1-aSyn-mice and wt littermates. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.
Publication Title
Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 293 Downloadable Samples
- Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain homeostasis. With aging, the frequency of polar HSCs decreases. Cell polarity in HSCs is controlled by the activity of the small RhoGTPase Cdc42. Here we demonstrate, using a comprehensive set of paired daughter cell analyses that include single cell 3D-confocal imaging, single cell transplants, single cell RNA-seq as well as single cell ATAC-seq, that the outcome of HSC divisions is strongly linked to the polarity status before mitosis, which is in turn determined by the level of the activity Cdc42 in stem cells. Aged apolar HSCs undergo preferentially self-renewing symmetric divisions, resulting in daughter stem cells with reduced regenerative capacity and lymphoid potential, while young polar HSCs undergo preferentially asymmetric divisions. Mathematical modeling in combination with experimental data implies a mechanistic role of the asymmetric sorting of Cdc42 in determining the potential of daughter cells via epigenetic mechanisms. Therefore, molecules that control HSC polarity might serve as modulators of the mode of stem cell division regulating the potential of daughter cells. Overall design: Sorted single cells were cultured with and without treatment in the presence of cytokines until first cell division (40-44hrs). The daughter cells were manually separated, washed with PBS and collected for RNA sequencing.
Publication Title
Aging alters the epigenetic asymmetry of HSC division.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
Publication Title
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
The airway epithelium represents a critical component of the human lung that helps orchestrate defences against respiratory tract viral infections, which are responsible for more than 2.5 million deaths/year globally. Innate immune activities of the airway epithelium rely Toll-like receptors (TLRs), nucleotide binding and leucine-rich-repeat pyrin domain containing (NLRP) receptors, and cytosolic nucleic acid sensors. ATP Binding Cassette (ABC) transporters are ubiquitous across all three domains of life – Archaea, Bacteria, and Eukarya – and expressed in the human airway epithelium. ABCF1, a unique ABC family member that lacks a transmembrane domain, has been defined as a cytosolic nucleic acid sensor that regulates CXCL10, interferon-b expression, and downstream type I interferon responses. We tested the hypothesis that ABCF1 functions as a dsDNA nucleic acid sensor in human airway epithelial cells important in regulating antiviral responses.
Publication Title
ABCF1 Regulates dsDNA-induced Immune Responses in Human Airway Epithelial Cells.
Sample Metadata Fields
Cell line
View Samples