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GSE6565
Homo sapiens
14 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Cartilage plays a fundamental role in the development of the human skeleton. Early in embryogenesis, mesenchymal cells condense and differentiate to chondrocytes to shape the early skeleton. Subsequently, the cartilage anlagen differentiate to form the growth plates, which are responsible for linear bone growth, and the articular chondrocytes, which facilitate joint function. However, despite the multiplicity of roles of cartilage during human fetal life, surprisingly little is known about its transcriptome. To address this, a whole genome microarray expression profile was generated using RNA isolated from 18-22 week human distal femur fetal cartilage and compared with a database of control normal human tissues aggregated at UCLA, termed CELSIUS. From the wealth of data, 161 cartilage-selective genes were identified, defined as genes significantly expressed in cartilage with low expression and little variation across a panel of 34 non-cartilage tissues. Among these 161 genes were cartilage-specific genes such as collagen genes and 25 genes which have been associated with skeletal phenotypes in humans and/or mice. Many of the other cartilage-selective genes do not have established roles in cartilage or are novel, unannotated genes. Quantitative RT-PCR confirmed the unique pattern of gene expression observed by microarray analysis. Defining the gene expression pattern for cartilage has identified new genes that may contribute to human skeletogenesis as well as provided further candidate genes for skeletal dysplasias. The data suggest that fetal cartilage is a complex and transcriptionally active tissue and demonstrate that the set of genes selectively expressed in the tissue has been greatly underestimated.
Publication Title
Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 228 Downloadable Samples
NextSeq 500
Description
Surface expression of the viral Envelope protein (Env) was used to enrich reactivated latent T cells producing HIV-RNA, and single cell RNASeq was performed to study gene expression differences between latent cells and controls. Overall design: Latent CD4+ T cells from virologically suppressed patients were reactivated in vitro and isolated using antibodies against HIV-1 Env. Single cell RNASeq was performed comparing reactivated latent cells with control, unpurified cells from the same donor and with cells actively infected in vitro using HIV-1(YU2).
Publication Title
Clonal CD4<sup>+</sup> T cells in the HIV-1 latent reservoir display a distinct gene profile upon reactivation.
Sample Metadata Fields
Subject
View Samples- Arabidopsis thaliana
- 29 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants respond to changes in the red:far red ratio (R:FR) of incident light. A reduction in this ratio (increase in FR) results in the Shade Avoidance Response (SAR) with associated changes in gene expression. The Phyotchrome-Interacting Factors (PIFs) are bHLH transcription factors known to be involved in the SAR. An analysis of changes in gene expression in WT and quadruple pif1pif3pif4pif5 (pifq; Leivar et al., 2008 (PMID 19920208)) mutant seedlings in response to an increase in FR should identify primary targets of PIF signaling.
Publication Title
Dynamic antagonism between phytochromes and PIF family basic helix-loop-helix factors induces selective reciprocal responses to light and shade in a rapidly responsive transcriptional network in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lower urinary tract malformations are among the most common congenital anomalies in humans. The urethral plate epithelium is an endodermal signaling region that plays an essential role in external genital development; however, little is known about the molecular identity of this cell population or the genes that regulate its activity. We aim to characterize differences in gene expression between the urethral plate epithelium and surrounding mouse genital tubercles during a crucial developmental period.
Publication Title
Molecular Characterization of the Genital Organizer: Gene Expression Profile of the Mouse Urethral Plate Epithelium.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
To investigate transcriptional differences between HCM and WT cells Overall design: Examination of HCM vs WT Cells, with 3 replicates of each sample
Publication Title
A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 74 Downloadable Samples
- NextSeq 500
Description
Single-cell expression profiling is a rich resource of cellular heterogeneity. While profiling every sample under study is advantageous, such workflow is time consuming and costly. We devised CPM - a deconvolution algorithm in which cellular heterogeneity is inferred from bulk expression data based on pre-existing collection of single-cell RNA-seq profiles. We applied CPM to investigate individual variation in heterogeneity of murine lung cells during in vivo influenza virus infection, revealing that the relations between cell quantities and clinical outcomes varies in a gradual manner along the cellular activation process. Validation experiments confirmed these gradual changes along the cellular activation trajectory. Additional analysis suggests that clinical outcomes relate to the rate of cell activation at the early stages of this process. These findings demonstrate the utility of CPM as a mapping deconvolution tool at single-cell resolution, and highlight the importance of such fine cell landscape for understanding diversity of clinical outcomes. Overall design: Lungs gene expression of Collaborative Cross mice taken 48h after the infection with either the influenza virus or PBS.
Publication Title
Cell composition analysis of bulk genomics using single-cell data.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The retinal pigment epithelium (RPE) provides vital support to photoreceptor cells and its dysfunction is associated with the onset and progression of age-related macular degeneration (AMD). Surgical provision of RPE cells may ameliorate AMD and thus it would be valuable to develop sources of patient-matched RPE cells for this application of regenerative medicine. We describe here the generation of functional RPE-like cells from fibroblasts that represent an important step toward that goal. We identified candidate master transcriptional regulators of RPEs using a novel computational method and then used these regulators to guide exploration of the transcriptional regulatory circuitry of RPE cells and to reprogram human fibroblasts into RPE-like cells. The RPE-like cells share key features with RPEs derived from healthy individuals, including morphology, gene expression and function, and thus represent a step toward the goal of generating patient-matched RPE cells for treatment of macular degeneration.
Publication Title
A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina Genome Analyzer II
Description
In adult cancers, epigenetic changes and aberrant splicing of the DNMT3B is commonly observed, and the pattern of gene methylation and expression has been shown to be modified by DNMT3B7, a truncated protein of DNMT3B. Much less is known about the mechanism of epigenetic changes in the pediatric cancer neuroblastoma. To investigate if aberrant DNMT3B transcripts alter DNA methylation, gene expression and tumor phenotype in neuroblastoma, we measured DNMT3B isoform expression in primary tumors and cell lines. Higher levels of DNMT3B7 were detected in differentiated ganglioneuroblastomas compared to undifferentiated neuroblastomas, suggesting that expression of DNMT3B7 may induce a less clinically aggressive tumor phenotype. To test this hypothesis, we investigated the effects of forced DNMT3B7 in neuroblastoma cells. We found that DNMT3B7 expression significantly inhibited neuroblastoma cell proliferation in vitro, and in neuroblastoma xenografts, DNMT3B7 decreased angiogenesis and tumor growth. DNMT3B7-positive cells had higher levels of total genomic methylation, and RNA-sequencing revealed a dramatic decrease in expression of FOS and JUN family members, AP1 complex components. Consistent with the established antagonistic relationship between AP1 expression and retinoic acid receptor activity, decreased proliferation and increased differentiation was seen in the DNMT3B7-expressing neuroblastoma cells following treatment with all trans retinoic acid (ATRA) compared to controls. Our results demonstrate that high levels of DNMT3B7 modify the epigenome in neuroblastoma cells, induce changes in gene expression, inhibit tumor growth, and increase sensitivity to ATRA. Further knowledge regarding mechanisms by which DNMT3B7 regulates gene methylation may ultimately lead to the development of therapeutic strategies that reverse the epigenetic aberrations that drive neuroblastoma pathogenesis. Overall design: DNMT3B7, a truncated DNMT3B isoform, was stably transfected into an N-type neuroblastoma cell line (LA1-55n) using a Tet-off inducible system. DNMT3B7 expressing cells were compared to vector control cells after 21 days of induction.
Publication Title
Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Evaluation of the airway transcriptome may reveal patterns of gene expression that are associated with clinical phenotypes of asthma. To define transcriptomic endotypes of asthma (TEA) we analyzed gene expression in induced sputum that correlate with phenotypes of disease. Gene expression was measured in sputum of subjects with asthma using Affymetrix HuGene ST 1.0 microarrays. Unsupervised clustering analysis of genes identified TEA clusters. Clinical characteristics were compared.
Publication Title
Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 84 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
Publication Title
Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples