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SRP043080
Homo sapiens
24 Downloadable Samples
IlluminaHiSeq2500
Description
Substantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-?B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals. Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.
Publication Title
Sample processing obscures cancer-specific alterations in leukemic transcriptomes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
To determine how aging impacts gene expression in hematopoietic stem cells (HSCs), human CD34+ cells from bone marrow (34BM) and mobilized stem cell products (34P38NPBSC) were examined using microarray-based expression profiling. Differential expression changes were confirmed by microarray comparisons of younger and older expanded T-cell populations.
Publication Title
Decreased IRF8 expression found in aging hematopoietic progenitor/stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 291 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Expression profiles of acute myeloid leukemia patient samples.
Publication Title
Identification of genes with abnormal expression changes in acute myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Acute myeloid leukemia (AML) is one of the most common and deadly forms of hematopoietic malignancies. We hypothesized that microarray studies could identify previously unrecognized expression changes that only occur only in AML blasts. We were particularly interested in those genes with increased expression in AML, believing that these genes may be potential therapeutic targets.
Publication Title
Identification of genes with abnormal expression changes in acute myeloid leukemia.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To identify gene expression that distinguishes hematopoietic cells that express PRAME from those that do not, normal CD34+ cells with forced PRAME expression were compared to cells without PRAME expression in culture over time (days 4, 7, 14) using Affymetrix HU-133A microarrays
Publication Title
The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Cryopreservation consists of preserving living cells or tissues at <-100C and has many applications in, for instance, stem cell and organ banking. Cryoprotectant agents, like ethylene glycol, are required for successful cryopreservation but have toxic side effects due to largely unknown mechanisms. In this work, we studied the toxicity of ethylene glycol in Human Umbilical Vein Endothelial Cells (HUVECs). Exposing cells to 60% ethylene glycol for two hours at 4C resulted in a slight decrease in cell growth, suggesting a modest toxicity of ethylene glycol and that HUVECs do not exhibit particular sensitivity to it. Gene expression analysis with whole genome micro-arrays revealed signatures indicative of a generalized stress response at 24 hours after stress and recovery at 72 hours, involving signaling pathways, glycoproteins, and genes involved in extracellular and transmembrane functions. These results reveal a new paradigm and signatures for future experiments in elucidating the toxicity effects of ethylene glycol in vascular endothelial cells.
Publication Title
Insights on cryoprotectant toxicity from gene expression profiling of endothelial cells exposed to ethylene glycol.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.
Publication Title
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HiSeq 2500
Description
Human naïve pluripotent stem cells (PSC) share features with pre-implantation epiblast. They thus provide an unmatched opportunity for characterising the developmental programme of pluripotency in Homo sapiens. Here we confirm that naïve PSC do not respond directly to germ layer induction, but must first acquire competence. Capacitation for multi-lineage differentiation occurs without exogenous growth factor stimulation and is facilitated by inhibition of Wnt signalling. Whole transcriptome profiling during this formative transition highlights dynamic changes in gene expression, affecting many cellular properties, including metabolism and epithelialisation. Notably, naïve pluripotency factors are exchanged for post-implantation factors, but competent cells remain devoid of lineage primed transcription. The gradual pace of transition for human naïve PSC is consistent with the timespan of primate development from blastocyst to gastrulation. Transcriptome trajectory during in vitro capacitation of human naïve cells tracks the progression of epiblast during embryogenesis in Macaca fascicularis, but shows greater divergence from mouse development. Thus the formative transition of naïve PSC in a simple culture system may recapitulate essential and specific features of pluripotency dynamics during an inaccessible period of human embryogenesis. Overall design: 2 lines of human naïve pluripotent stem cells (embryo-derived HNES1 and chemically reset cR-H9-EOS) were cultured in N2B27 and 2uM XAV939 for 10 days. After that the cells were split into two conditions: N2B27 + 2uM XAV939 + 3ng/ml Activin A + 10ng/ml FGF2 (XAF), or E8 medium, for extended maintenance. The experiment was performed in biological triplicates for each cell line. RNAseq was performed with the cells on day 0, 1, 2, 3, 7, 10, when the cells were cultured in XAV939; and one time point after transfer to maintenance conditions, at not less than 22 days of culture from the start of the experiment. Conventional hES cell line H9-EOS, which was a parental line for the chemically reset cR-H9-EOS was used as a control (in biological triplicate).
Publication Title
Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We compared the gene expression of A549 cells following 24 and 48 hours of treatment with a no-observed-effect level dose of cisplatin. The objective of the study is to identify genes that are differentially expressed in response to sub-lethal doses of cisplatin. This study helps identify not only treatment responses but also changes in gene expression that may confer cytoprotective mechanisms that allow these cells to survive treatment and to develop treatment resistance.
Publication Title
Combined Use of Gene Expression Modeling and siRNA Screening Identifies Genes and Pathways Which Enhance the Activity of Cisplatin When Added at No Effect Levels to Non-Small Cell Lung Cancer Cells In Vitro.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples