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Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells consisting of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous) cells. Because of its rare incidence, lack of suited model systems and technical limitations analysis was only performed on bulk tumor mass neglecting its heterogeneous composition. We aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Secondly, we intended to clarify whether the observed cell types are derived from genetically distinct clones or rather represent different phenotypes. Using the chordoma cell line MUG-Chor1 we monitored morphological changes via time lapse experiments. We isolated pure fractions of each phenotype by means of laser microdissection or micromanipulation allowing phenotype-specific analysis. Pools of 100 cells each were genetically profiled after whole genome amplification by array comparative genomic hybridization. For expression analysis 20 cells each were subjected to whole transcriptom amplification, forwarded to RNA microarray analysis and qRT-PCR. Time lapse analysis unveiled small non-vacuolated cells to develop into large physaliferous cells via intermediate cells containing an increasing amount of vacuoles. Furthermore, we showed small and large physaliferous cells to proliferate at the same rate but intermediate cells to be the most proliferating cell phenotype. Small non-vacuolated and large physaliferous cells showed identical copy number variations. Despite their obvious morphological disparities we detected only modest changes in over all gene expression. However, verification of candidate genes yielded significant up-regulation of ALG11 (700-fold), PPP2CB (18.6-fold), and UCHL3 (18.7-fold) in large physaliferous cells.
Publication Title
Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.
Sample Metadata Fields
Cell line
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SRP162274- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Triple-Negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with poor prognosis due to its propensity to form metastases. Unfortunately, the current treatment options are limited to chemotherapy such that identification of actionable targets are needed. The receptor tyrosine kinase AXL plays a role in the tumor cell dissemination and its expression in TNBC correlates with poor patients? survival. Here, we explored whether exploiting an AXL knockdown gene signature in TNBC cells may offer an opportunity for drug repurposing. To this end, we queried the PharmacoGx pharmacogenomics platform with an AXL gene signature which revealed Phenothiazines, a class of Dopamine Receptors antagonists (Thioridazine, Fluphenazine and Trifluoperazine) typically used as anti-psychotics. We next tested if drugs may be active to limit growth and metastatic progression of TNBC cells, similarly to AXL depletion. We found that the Phenothiazines were able to reduce cel l invasion, proliferation and viability, and also increased apoptosis of TNBC cells in vitro. Mechanistically, these drugs did not affect AXL activity but instead reduced PI3K/AKT/mTOR and ERK signaling. When administered to mice bearing TNBC xenografts, these drugs showed were able to reduce tumor growth and metastatic burden. Collectively, these results suggest that these antipsychotics are novel anti-tumor and anti-metastatic agents that could potentially be repurposed, in combination with standard chemotherapy, for use in TNBC. Overall design: RNA-seq of the Triple Negative Breast Cancer cell line MDA-MB-231 treated with siCt or siAXL Differential gene expression profile between MDA-MB-231 siCt and siAXL by RNA sequencing (Illumina HiSEq 2000)
Publication Title
AXL knockdown gene signature reveals a drug repurposing opportunity for a class of antipsychotics to reduce growth and metastasis of triple-negative breast cancer.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The pancreatic beta cells are the only cells that can produce insulin in response to prevailing glycemia. The development of beta cells was found to be depending on the activity of a complex genetic network. Overexpression of transcriptional factor MafK in beta cells have resulted in impairment of thier functions and suppressed insulin secretion and increased the severity of beta cell loss resulting in an overt diabetes.
Publication Title
β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 4000
Description
Cellular diversity within tumors and reduced lineage commitment can undermine targeted therapy by increasing the probability of treatment-resistant populations. Using single-cell RNA-seq, we analyzed cellular diversity and lineage in medulloblastomas in transgenic, medulloblastoma-prone mice, and responses to the SHH-pathway inhibitor vismodegib. Overall design: Drop-Seq single-cell transcriptome sequencing of 15 mice: 5 Wild Type cerebella, 5 Drug-treated cerebellar tumors and 5 vehicle-treated cerebellar tumros.
Publication Title
scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 66 Downloadable Samples
- IlluminaHiSeq1500
Description
The goal of this study is to simultaneously interrogate host and parasite gene expression programs in human macrophages infected with the intracellular parasites from the genus Leishmania. We conducted high-resolution sequencing of the transcriptomes of human macrophages infected with Leishmania spp. using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes at various time points post-infection, enabling us to identify co-expression patterns that correlate with the biology of the parasite and to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. This study provides a solid framework for future functional and genomic studies of leishmaniasis as well as intracellular pathogenesis in general.
Publication Title
Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 7 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy as well as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring.
Publication Title
Effects of moderate drinking during pregnancy on placental gene expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 1500
Description
Macrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and alterations in mRNA levels were analyzed. We identified three transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands, in the presence of three different “reprogramming” signals; high density immune complexes (IC), prostaglandin E2 (PGE2), or adenosine (Ado). All three of these cell populations produced higher levels of transcripts for IL-10, and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1Beta, IL-6, and IL-12. All three macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore we consider each to have immunoregulatory activity. This immunoregulatory activity occurred equally well in macrophages from stat6-deficient mice. The lack of STAT6 did not affect macrophages’ ability to reciprocally change cytokine production or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These immunoregulatory macrophages are transcriptionally and functionally related, and quite distinct from macrophages treated with IL-4.
Publication Title
The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- IlluminaGenomeAnalyzerII, IlluminaHiSeq2000
Description
Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape of circulating RNA in human subjects. By focusing on tissue-specific genes, we were able to identify the relative contributions of these tissues to circulating RNA and monitor changes during tissue development and neurodegenerative disease states.
Publication Title
Noninvasive in vivo monitoring of tissue-specific global gene expression in humans.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We employed high throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA, and to monitor changes in tissue development and health.
Publication Title
Noninvasive in vivo monitoring of tissue-specific global gene expression in humans.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 63 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Plasma cells (PCs) as effectors of humoral immunity produce immunoglobulins to match pathogenic insult. However, emerging data suggests more diverse roles for PCs as regulators of immune and inflammatory responses via secretion of factors other than immunoglobulins. The extent to which such responses are pre-programmed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. Here we dissect the impact of IFNs on the regulatory networks of human plasma cells. We show that core PC programs are unaffected, while PCs respond to IFNs with distinctive transcriptional responses. The ISG15-system emerges as a major transcriptional output induced in a sustained fashion by IFN- in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active SLE. Thus ISG15-secreting PCs represent a distinct pro-inflammatory PC subset providing an immunoglobulin-independent mechanism of PC action in human autoimmunity
Publication Title
Network Analysis Identifies Proinflammatory Plasma Cell Polarization for Secretion of ISG15 in Human Autoimmunity.
Sample Metadata Fields
Sex, Specimen part
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