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SRP034892
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
Remembrances of traumata range among the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that in mice successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes as revealed by whole genome RNA sequencing, which is accompanied by higher metabolic, synaptic and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. Overall design: 3 biological replicates per group were analyzed. The material analyzed was whole hippocampi from one brain hemisphere, from which total RNA was extracted.
Publication Title
Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Molecular profiling of infiltrating monocyte-derived macrophages versus resident kupffer cells following acute liver injury
Publication Title
Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury.
Sample Metadata Fields
Specimen part, Disease, Time
View Samples- Homo sapiens
- 332 Downloadable Samples
- Illumina HiSeq 4000
Description
Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on a- and ß-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between a- and ß-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 a, 105 ß, 6 d endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between a- and ß-cells. 10 genes showed concordant expression as reported in rodents, while FAM46A was significantly discordant. Comparing our East-Asian data with data from primarily European subjects, we replicated several genes implicated in nuclear receptor activations, acute phase response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling. Additionally, we identified protein ubiquitination to be associated among East-Asian ß-cells. We report on East-Asian a- and ß-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian ß-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis. Overall design: 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. 223 islet-cells remained after samples QC, and these cells were used for subsequent analyses. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. We identified 118 a and 105 ß endocrine cells in our dataset.
Publication Title
Single-cell transcriptomics of East-Asian pancreatic islets cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- IlluminaHiSeq2000
Description
To identify transcripts altered upon LIN-41 knockdown, we transfected either a control siRNA or one of two different LIN-41 siRNAs into human embryonic stem cells and collected total RNA 72 hours after transfection. Overall design: We compared transcript levels between control siRNA or LIN-41 siRNA treated cells.
Publication Title
The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ovarian cancer is the most lethal malignancy in the United States. In the year 2012, there will be an estimated 22,280 new cases and 15,500 deaths from ovarian cancer in the country (Siegel et al., 2012). While studies on ovarian cancer pathogenesis were mainly focused on the epithelial component of the tumor, understanding in the role of cancer associated fibroblasts (CAFs) in ovarian cancer progression is limited. We hypothesized that comparing the gene expression profiles of different components from laser capture microdissected ovarian tissue will allow us to identify an ovarian CAFs specific gene signature which accounts for the supportive role of CAFs in ovarian cancer progression. In this study, gene expression profiling was completed for 31 cancer stroma samples and 32 samples of epithelial component from high grade serous ovarian cancer patients. 8 microdissected normal ovarian stroma and 6 normal human ovarian surface epithelium (HOSE) samples were also included in the study. By comparing the expression data from cancer stroma against that from normal stroma, cancer cells and HOSE, we identified a set of differential expressed genes in ovarian CAFs which showed correlation with cancer patient survival. Further study on these genes can reveal their roles in ovarian cancer progression and pathogenesis. Ultimately, ovarian CAFs specified genes identified in this study may aid in the classification and enhancement of patient outcome.
Publication Title
TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Ovarian cancer cells are known to have diminished response to TGF-beta, but it remains unclear whether TGF-beta can modulate ovarian cancer cell growth in an indirect manner through cancer-associated fibroblasts (CAFs). Using transcriptome profiling analyses on TGF-beta-treated ovarian fibroblasts, we identified a TGF-beta-responsive gene signature in ovarian fibroblasts. Identifying TGF-beta-regulated genes in the ovarian microenvironment helps in understanding the role of TGF-beta in ovarian cancer progression.
Publication Title
TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Currently patients are treated by surgical cytoreductive surgery with the aim of reducing tumor burden to microscopic disease followed by adjuvant combined treatment with a platinum and taxane containing chemotherapy, which affords 80% of patients an initial complete response. However, Abdominal and pelvic recurrence rates are high and response to further chemotherapy is limited. Attempts at introducing biologic therapeutic agents to improve outcome in this disease are ongoing, while prognostic or predictive biomarkers that can stratify patients for treatment are still lacking. Using transcriptome profiling of microdissected tissue samples from high-grade serous ovarian cancer patients, we identified a cancer associated fibroblast (CAF) specific gene signature. Versican, which encodes a extracellular matrix protein, was one of the identified genes which demonstrated up-regulation in cancer stroma. To investigate the function roles, signaling machanism and the effect of versican treatment on ovarian cancer cells, transcriptome profiling of versican treated OVCA433 high-grade serous ovarian cancer cells was performed.
Publication Title
TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Analysis of gene expression levels in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions
Publication Title
Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Inflammasome activation is critical for host defense against various microbial infections. Activation of the NLRC4 inflammasome requires detection of flagellin or type III secretion system (T3SS) components by NLR family apoptosis inhibitory proteins (NAIPs); yet how this pathway is regulated is unknown. Here we found that interferon regulatory factor 8 (IRF8) is required for optimal activation of the NLRC4 inflammasome in bone marrow-derived macrophages infected with Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and Pyrin inflammasomes. IRF8 governs the transcription of Naips to allow detection of flagellin or T3SS proteins to mediate NLRC4 inflammasome activation. Furthermore, we found that IRF8 confers protection against bacterial infection in vivo, owing to its role in inflammasome-dependent cytokine production and pyroptosis. Altogether, our findings suggest that IRF8 is a critical regulator of NAIPs and NLRC4 inflammasome activation for defense against bacterial infection.
Publication Title
IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation.
Sample Metadata Fields
No sample metadata fields
View Samples