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GSE112260
Homo sapiens
13 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Background: Macrophages are important cells in pathogenesis of obstructive lung diseases including asthma and chronic obstructive pulmonary disease (COPD). The aim of the study was a multivariate, genetic, comparative analysis of macrophages from patients with asthma and COPD.
Publication Title
Genetic characterization of macrophages from induced sputum of patients with asthma and chronic obstructive pulmonary disease.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 144 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background. Most colorectal cancers (CRC) arise in a progression through adenoma to carcinoma phenotypes as a consequence of altered genetic information. Clinical progression of CRC may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. Methodology/Principal Findings. Studies were performed on normal mucosa, adenoma, and CRC samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. RNA was isolated from 105 macro- and 40 microdissected specimens. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data were generated using two normalization algorithms: MAS5 and GCRMA with LVS. The data were evaluated using pair-wise comparisons and data decomposition into SVD modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Based on a consensus of the results obtained by two tissue handling procedures, two normalization algorithms, and two probe set sorting criteria, we identified six KEGG signaling and metabolic pathways (cell cycle, DNA replication, p53 signaling pathway, purine metabolism, pyrimidine metabolism, and RNA polymerase) that are significantly altered in both macro- and microdissected tumor samples compared to normal colon. On the other hand, pathways altered between benign and malignant tumors were identified only in the macrodissected tissues. Conclusion/Significance. Multidirectional analyses of microarray data allow the identification of essential signaling alterations underlying CRC development. Although the proposed strategy is computationally complex and laborintensive, it may reduce the number of false results.
Publication Title
Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional profiles of HCMV or Mock infected neonatal and adult were anayzed
Publication Title
IL-12 and type I IFN response of neonatal myeloid DC to human CMV infection.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 175 Downloadable Samples
Illumina HiSeq 2500
Description
To better understand human spermatogonial stem cells (SSCs), we profiled their transciptome and epigenome, which revealed the mechanism how human SSCs regulates their self-renewal versus differentiation dermination, as well as how latent pluripotency is established in human SSCs. Remarkly, we discovered signaling pathways (e.g. LIF, BMP, WNT) that differentially regulated self-renewal vesus differentiation in SSCs. We also discovered that SSCs repress core pluripotent factors (Sox2, Pou5f1 and Nanog) yet activate ancillary factors (e.g. Klf4, Mbd3, Tcf3, Sall4) transcriptionally and epigenetically. Overall design: Using SSEA4 as self-renewal marker and Kit as differentiating marker, we isolated self-renewal and differentiation SSCs by magnetic antibody cell sorting (MACS). SSEA4+ or Kit+ cells were loaded into 5-10 µm integrated fluidic circuits (IFCs) using Fluidigm C1 instrument. Single cells in IFCs were lysed and total RNA was harvested for polyadenylation selection, reverse transcription and PCR amplification. Library constructions were performed according to Fluidigm Library preparation with Nextera XT protocol and sequenced on a 50-cycle single end run.
Publication Title
Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
To better understand human spermatogonial stem cells (SSCs), we profiled their transciptome and epigenome, which revealed the mechanism how human SSCs regulates their self-renewal versus differentiation dermination, as well as how latent pluripotency is established in human SSCs. Remarkly, we discovered signaling pathways (e.g. LIF, BMP, WNT) that differentially regulated self-renewal vesus differentiation in SSCs. We also discovered that SSCs repress core pluripotent factors (Sox2, Pou5f1 and Nanog) yet activate ancillary factors (e.g. Klf4, Mbd3, Tcf3, Sall4) transcriptionally and epigenetically. Overall design: Using SSEA4 as self-renewal marker and Kit as differentiating marker, we isolated self-renewal and differentiation SSCs by magnetic antibody cell sorting (MACS). Total RNA were extracted from those populations, and standard RNA sequencing libraries were prepared for sequnecing on a 50-cycle single end run.
Publication Title
Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The goal of this study was to identify the transcriptional mechanisms involved in the activation of the immune system by QS-21, a triterpene glycoside purified from the bark of Quillaja saponaria which has adjuvant activity in vivo. Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the Malaria and Zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T cell priming by QS-21 as revealed by the decrease in antigen-specific T cell response in Batf3/ mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans
Publication Title
Central Role of CD169<sup>+</sup> Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in KIT or PDGFRA of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations.
Publication Title
Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression.
Sample Metadata Fields
Sex, Specimen part, Disease stage
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Tristetraprolin (TTP, encoded by Zfp36) regulates the mRNA stability of several important cytokines. Due to the critical role of this RNA-binding protein in the control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL-23 by myeloid cells such as macrophages or dendritic cells. Here, we generated mice with conditional deletion of TTP in keratinocytes. These mice developed exacerbated inflammation in the imiquimod-induced psoriasis model. Furthermore, these mice progressively developed a spontaneous pathology with systemic inflammation, psoriatic-like skin lesions and dactylitis. Finally, we provide evidence that keratinocyte-derived TNF productin drives the different pathological features. In summary, these findings expand current views on the initiation of psoriasis and related arthritis by revealing the keratinocyte-intrinsic role of TTP.
Publication Title
Tristetraprolin expression by keratinocytes controls local and systemic inflammation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Human adult spermatogenesis involves a balance of spermatogonial stem cell self renewal and differentiation, alongside complex germline-niche interactions. To better understand, we performed single cell RNA sequencing of ~7000 testis cells from three healthy men of peak reproductive age. Our analyses revealed multiple distinctive transcriptional 'states' of self-renewing and differentiating spermatogonia, the cellular stages of gametogenesis, five niche cells (Leydig, Myoid, Sertoli, Endothelial, macrophage) and insights into germline-niche communication. Spermatogenesis was reconstructed computationally, which identified sequential coding, noncoding, and repeat-element transcriptional signatures. A new, developmentally early and likely quiescent spermatogonial state is identified (GFRA1-/ETV5-/ID4+/UTF1+/FGFR3+). Notably, certain epigenetic features combined with nascent transcription analyses suggest considerable plasticity within certain spermatogonial populations/states. Key findings were validated via RNA and protein staining. Taken together, we provided the first “Cell Atlas” of the adult human testis, and provide multiple new insights into germ cell development and germ cell – niche interaction. Overall design: We isolated single testicular cell from two infant (13 months old). Two technical replicates were performed for each individual.
Publication Title
The adult human testis transcriptional cell atlas.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples