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GSE112229
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The major surface glycoprotein (Msg) is the most abundant surface protein of Pneumocystis species. Given that Msg is present on both the cyst and trophic form of Pneumocystis, and dendritic cells play a critical role in initiating host immune responses, we undertook studies to examine activation of bone marrow-derived myeloid dendritic cells by Msg purified from P. murina. Incubation of dendritic cells with Msg did not lead to increased expression of CD40, CD80, CD86, or MHCII, or increased secretion of any of 10 cytokines. Microarray analysis identified very few differentially expressed genes. In contrast, LPS activated dendritic cells by all of these assays. However, Msg did bind to mouse mannose macrophage receptor and human DC-SIGN, two C-type lectins expressed by dendritic cells that are important in recognition of pathogen-associated high mannose glycoproteins. Deglycosylation of Msg demonstrated that this binding was dependent on glycosylation. These studies suggest that Pneumocystis has developed a mechanism to avoid activation of dendritic cells, potentially by the previously identified loss of genes that are responsible for the high level of protein mannosylation found in other fungi.
Publication Title
The Major Surface Glycoprotein of Pneumocystis murina Does Not Activate Dendritic Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
The retinal pigment epithelial (RPE) cell line ARPE-19 provides a widely-used alternative to native RPE. However, retention of the native RPE phenotype becomes problematic after multiple passages. We wished to determine if suitable culture conditions and differentiation could restore RPE-appropriate gene expression to ARPE-19. ARPE-19 cells at passages p9 to p12, grown in DMEM containing high glucose and pyruvate with 1% fetal bovine serum, were differentiated for up to 4 months. Using RNA-Seq, we compared the transcriptome of ARPE-19 cells kept in long-term culture with those cultured for 4 days. The 4 month cells developed the classic native RPE phenotype with heavy pigmentation. RNA-Seq analysis provided a comprehensive view of the relative abundance and differential expression of genes in the 4 month cells. Of the 16,757 genes with detectable signals, nearly 2435 genes were upregulated, and 931 genes were down-regulated with a fold change differences of 2 or more. Genes characteristic of RPE, including RPE65, RDH5 and RDH10, were greatly increased in ARPE-19 cells maintained at confluence for 4 months. Comparison with microarray data sets from human primary cell lines revealed important overall similarities in expression of "signature" genes. The results of this study demonstrate that ARPE-19 cells can express genes specific to native human RPE cells when appropriately cultured, and thus, can provide a relevant system to study differentiated cellular functions of RPE in vitro. Overall design: RNA-Seq profiles of ARPE-19 cells grown for 4 days or 4 months; triplicate replicates were sequenced.
Publication Title
Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether -1,3 glucans are masked by surface proteins in Pneumocystis, and what role -glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, -1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using Q-PCR and microarray techniques, we demonstrated in a mouse model of PCP that treatment with caspofungin, an inhibitor of -1,3 glucan synthesis, for 21 days, decreased expression of a broad panel of inflammatory markers, including IFN-, TNF-, IL-1, IL-6, and multiple chemokines/chemokine ligands. Thus, -glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.
Publication Title
β-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have performed whole genome expression arrays covering over 47000 transcripts comparing the transcriptional profile of NKp80+ to NKp80- CD8+ CCR7- alpha beta T cells. A highly similar global gene expression profile was observed between both memory phenotype T cell subsets. Interestingly, the majority of differentially expressed genes are immune-associated. NKp80+ cells contained markedly increased levels of transcripts encoding for MHC class I and II molecules and for numerous members of the KIR family. Also other NK-related transcripts were more abundantly expressed in the NKp80+ subset. With regards to cytokines, chemokines and their receptors, transcripts important for homeostasis and proliferation are expressed differently. Also transcripts encoding for adhesion molecules are present at different levels in both T cell subsets. Further cytotoxic effector molecules are expressed differently.
Publication Title
NKp80 defines and stimulates a reactive subset of CD8 T cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 910 Downloadable Samples
- Illumina HiSeq 2500
Description
Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA profile for timecourse of neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124).
Publication Title
Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 93 Downloadable Samples
- Illumina HiSeq 2500
Description
Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA interacting protein immunoprecipitation with AGO2 for miR-124 target enrichment from neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124) and subsequent sequencing.
Publication Title
Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The study aimed to resolve the mechanisms of protective actions of MMP-8 in oral tongue squamous cell carcinoma.
Publication Title
The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The Ca2+/calmodulin-dependent kinase II is expressed in smooth muscle and believed to mediate intracellular calcium handling and calcium-dependent gene transcription. CaMKII is activated by Angiotensin-II.
Publication Title
Calcium/calmodulin-dependent kinase II inhibition in smooth muscle reduces angiotensin II-induced hypertension by controlling aortic remodeling and baroreceptor function.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitochondrial calcium is an important second-messenger controlling fight-or-flight responses in the heart. The molecular identity of MCU (Mitochondrial Calcium Uniporter) was recently discovered allowing us to test this hypothesis in vivo by expressiing a myocardial delimited dominant negative form of MCU.
Publication Title
Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Global deficiency of catalytic subunit Ppp3cb, and tissue-specific ablation of regulatory subunit Ppp3r1 from skeletal muscle but not adipose tissue or liver led to protection from high-fat diet induced obesity and comorbid sequel.
Publication Title
Calcineurin Links Mitochondrial Elongation with Energy Metabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples