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Mus musculus
16 Downloadable Samples
Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Infiltrating monocyte derived macrophages (MDMs) and resident microglia dominate CNS injury sites. We show that MDMs and microglia can directly communicate to modulate each others function. Also, the presence of MDMs in CNS injury suppresses microglia-mediated phagocytosis and inflammation. We suggest that macrophages infiltrating the injured CNS provide a mechanism to control acute and chronic microglia-mediated inflammation, which could otherwise drive damage in a variety of CNS conditions.
Publication Title
Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Retinal detachment is a major cause of blindness due to penetrating trauma and ocular inflammation, and is often observed in many patients following cataract extraction surgery. When the retinal photoreceptors detach from their epithelium, stress signals and apoptotic pathways are initiated that will lead to loss of vision, however accelerating the reattachment of these cells can prevent photoreceptor death and subsequent vision loss. To determine the genes involved in this process, we performed a microarray screen using a mouse model or retinal detachment in conjunction with a P2Y2 agonist previously demonstrated to hasten retinal reattachment.
Publication Title
Expression profiling after retinal detachment and reattachment: a possible role for aquaporin-0.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE42955- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Global gene expression is altered in heart failure. This syndrome can be caused by cardiovascular diseases, including dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy, viral or toxic myocarditis, hypertension, and valvular diseases.
Publication Title
Differential gene expression of cardiac ion channels in human dilated cardiomyopathy.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Subject
View Samples- Homo sapiens
- 656 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 529 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Sub-clinical acute rejection (subAR) in kidney transplant recipients (KTR) leads to chronic rejection and graft loss. Non-invasive biomarkers are needed to detect subAR. 307 KTR were enrolled into a multi-center observational study. Precise clinical phenotypes (CP) were used to define subAR. Differential gene expression (DGE) data from peripheral blood samples paired with surveillance biopsies were used to train a Random Forests (RF) model to develop a gene expression profile (GEP) for subAR. A separate cohort of paired samples was used to validate the GEP. Clinical endpoints and gene pathway mapping were used to assess clinical validity and biologic relevance. DGE data from 530 samples (130 subAR) collected from 250 KTR yielded a RF model: AUC 0.85; 0.84 after internal validation with bootstrap resampling. We selected a predicted probability threshold favoring specificity and NPV (87% and 88%) over sensitivity and PPV (64% and 61%, respectively). We tested the locked model/threshold on a separate cohort of 138 KTR undergoing surveillance biopsies at our institution (rejection 42; no rejection 96): NPV 78%; PPV 51%; AUC 0.66. Both the CP and GEP of subAR within the first 12 months following transplantation were independently associated with worse graft outcomes at 24 months, including de novo donor-specific antibody (DSA). Serial GEP tracked with response to treatment of subAR. DGE data from both cohorts mapped to gene pathways indicative of allograft rejection.
Publication Title
Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 308 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Early diagnosis of transthyretin (TTR) amyloid diseases remains challenging because of variable disease penetrance. Currently, patients must have an amyloid positive tissue biopsy to be eligible for disease modifying therapies. Early diagnosis is often difficult because the patient exhibits apparent symptoms of polyneuropathy or cardiomyopathy, but has a negative amyloid biopsy. Thus, there is a pressing need for more objective, quantitative diagnostics and biomarkers of TTR-aggregation-associated polyneuropathy and cardiomyopathy. This is especially true in the context of clinical trials demonstrating significant disease modifying effects, e.g. when the TTR tetramer stabilizer tafamidis was administered to familial amyloid polyneuropathy (FAP) patients early in the disease course. When asked if the findings of the tafamidis registration trial were sufficiently robust to provide substantial evidence of efficacy for a surrogate endpoint that is reasonably likely to predict a clinical benefit the advisory committee said yes, but the FDA rejected the tetramer stabilization surrogate biomarker required for orphan tafamidis approvalhence, acceptable biomarkers are badly needed. Herein, we explored whether peripheral blood cell mRNA expression profiles could differentiate symptomatic from asymptomatic V30M FAP patients, and if such a profile would normalize upon tafamidis treatment. We demonstrate that blood cell gene expression patterns reveal sex-independent as well as male and female specific inflammatory signatures in symptomatic FAP patients, but not in asymptomatic carriers, that normalize in FAP patients 6 months after tafamidis treatment. Thus these signatures have potential both as an early diagnostic and as a surrogate biomarker for measuring response to treatment in FAP patients.
Publication Title
Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 273 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Rationale: Interstitial fibrosis and tubular atrophy (IFTA) is found in ~25% of 1-year biopsies post-transplant(1, 2). It correlates with decreased graft survival when histological evidence of inflammation is present.(3-5) Identifying the etiology of IFTA is important because longterm graft survival has not changed as expected given improved therapies and a dramatically reduced incidence of acute rejection.(6-8) Methods: Gene expression profiles of 234 samples were obtained with matching clinical and outcome data (7 transplant centers). 81 IFTA samples were divided into subphenotypes by the degree of inflammation on histology: IFTA with acute rejection (AR), IFTA with inflammation and IFTA without inflammation. Samples with AR (n=54) and normally functioning transplants (TX; n=99) were used in comparisons. Conclusions: Gene expression profiling of all IFTA phenotypes were strongly enriched for cAR gene dysregulation pathways, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. We also found that the relative expression of AR-affiliated genes correlated with future graft loss in IFTA samples without inflammation. We conclude that undetected and/or undertreated immune rejection is leading to IFTA and graft failure.
Publication Title
Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based disease models in which the observed phenotype depends on proper XCI or imprinting, and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting.
Publication Title
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 179 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we employed transcriptome mRNA profiling of whole blood and purified CD4, CD8 T cells, B cells and monocytes in tandem with high-throughput flow cytometry in 10 kidney transplant patients sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. We then mechanistically deconvoluted the early post-transplant immune response. The flow cytometry data confirms depletion of specific cell subsets in response to ATG induction and immunosuppression with sustained decreases in CD4 as well as CD8 cell subsets. A series of T cell activation markers were expressed from Pre-Tx to 12 weeks indicating the evolution of immunity including expansion of CD45RO+CD62L- effector memory cells. Serial whole blood transcript monitoring demonstrated over 2000 differentially expressed genes, with over 80 percent down-regulated Post-Tx. However, cell subset analysis revealed a unique spectrum of subset-specific gene expression with time-dependent changes, with contrasting significant Post-Tx gene upregulation. Our results provide a unique view of the complex evolution of immune/inflammatory molecular networks marking the early post transplant immune response. A critical finding is that analysis of the constituent blood cell subsets provides an entirely new level of detail revealing the nature of this process, effectively deconvoluting the changes that are otherwise lost in the noise of cellular complexity of whole blood.
Publication Title
Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.
Sample Metadata Fields
Time
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