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GSE27447
Homo sapiens
19 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of beta-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer.
Publication Title
FZD7 has a critical role in cell proliferation in triple negative breast cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 99 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Site-specific programming of the host epithelial transcriptome by the gut microbiota.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Differential expression of genes between Arabidopsis WRKY18/40 knock out and wild type plants, after 8 h post inoculation of powdery mildew pathogen.
Publication Title
Transcriptional reprogramming regulated by WRKY18 and WRKY40 facilitates powdery mildew infection of Arabidopsis.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
To identify the miRNAs that are differentially expressed and secreted between the MDA-MB-231 metastatic breast cancer cells and the MCF-10A non-cancerous human mammary epithelial cells, we profiled the cellular and exosomal small RNAs (between 17 and 52 nt) isolated from these two cell lines by Solexa deep sequencing. MiRNAs that are significantly different between the two cell lines are identified. Overall design: RNA was extracted from cultured MDA-MB-231 and MCF-10A cells or purified exosomes secreted by these cells, and subjected to library construction and Solexa deep sequencing.
Publication Title
Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Bone marrow samples from normal adult male donors were collected into EDTA. Red cells were removed by ammonium chloride lysis. Leukocytes were washed in SM buffer and CD34+ cells were separated from CD34- cells using an AutoMACS device and anti-CD34 immunomagnetic beads (Miltenyi Biotec), according to manufacturers instructions. For mature cell populations, CD34- cells were FACS purified according to the following immunophenotypes, with 7-AAD used to exclude dead cells: Neutrophils: side scatter high CD15+ CD16+. Monocytes: side scatter low-intermediate CD14+ CD16- CD15-. See also Huang et al., 2014.
Publication Title
Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Given the importance of deregulated phosphoinositide (PI) signaling in leukemic hematopoiesis, genes coding for proteins that regulate PI metabolism may have significant and as yet unappreciated roles in leukemia. We performed a targeted knockdown screen of PI modulator genes in human AML cells and identified candidates required to sustain proliferation or prevent apoptosis. One of these, the lipid kinase phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A) regulates cellular levels of phosphatidylinositol-5-phosphate (PtsIns5P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). We found PIP4K2A to be essential for the clonogenic and leukemia-initiating potential of human AML cells, and for the clonogenic potential of murine MLL-AF9 AML cells. Importantly, PIP4K2A is also required for the clonogenic potential of primary human AML cells. Its knockdown results in accumulation of the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, G1 cell cycle arrest and apoptosis. Both CDKN1A accumulation and apoptosis were partially dependent upon activation of the mTOR pathway. Critically, however, PIP4K2A knockdown in normal hematopoietic stem and progenitor cells, both murine and human, did not adversely impact either clonogenic or multilineage differentiation potential, indicating a selective dependency which we suggest may be the consequence of the regulation of different transcriptional programmes in normal versus malignant cells. Thus, PIP4K2A is a novel candidate therapeutic target in myeloid malignancy.
Publication Title
A targeted knockdown screen of genes coding for phosphoinositide modulators identifies PIP4K2A as required for acute myeloid leukemia cell proliferation and survival.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- NextSeq 500
Description
The Iroquois homeodomain transcription factor gene IRX3 is highly expressed in the developing nervous system, limb buds and heart. In adults, expression levels specify risk of obesity. We now report a significant functional role for IRX3 in human acute leukemia. While transcript levels are very low in normal human bone marrow cell populations, high level IRX3 expression is observed in ~30% of patients with acute myeloid leukemia (AML), ~50% of patients with T-acute lymphoblastic leukemia and ~20% of patients with B-acute lymphoblastic leukemia, typically in association with high levels of HOXA9. Expression of IRX3 alone was sufficient to immortalise murine bone marrow stem and progenitor cells, and induce T- and B-lineage leukemias in vivo with incomplete penetrance. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine bone marrow stem and progenitor cells substantially enhanced the morphologic and phenotypic differentiation block of the resulting AMLs by comparison with Hoxa9-only leukemias, through suppression of a myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 modulates the cellular consequences of HOX gene expression to enhance differentiation block in human AML. Overall design: Murine acute myeloid leukemias - 3 samples from separate mice with AML initiated by HOXA9 and 3 samples from separate mice with AML initiated by HOXA9 and IRX3 coexpression
Publication Title
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina Genome Analyzer II
Description
We generated knock-in mice expressing GFP under the control of the endogenous GIP (Glucose-dependent Insulinotropic Polypeptide) promoter that enable the isolation of a purified population of small intestine K cells. Using RNA-Seq, we comprehensively characterized the transcriptomes of GIP-GFP cells as well as the entire enteroendocrine lineage derived from Neurogenin3 (Ngn3)-expressing progenitors. Overall design: We interrogated the whole transcriptome of FACS-isolated small intestine GIPGFP cells using high-throughput mRNA sequencing. We also obtained the global gene expression patterns of the entire enteroendocrine cell lineage as well as the non-enteroendocrine cell population, comprising enterocytes, goblet cells and Paneth cells. To achieve this, small intestine epithelial cells from male mice resulting from the breeding of Neurogenin3 (Ngn3)-Cre mice with ROSA26-LoxP-STOP-LoxP-tomato indicator mice were isolated based on Tomato fluorescence and negative staining for CD45. Due to the small cell numbers, we constructed each of the three RNA-Seq libraries (GIPGFP, Ngn3TOMATO, and Ngn3-) using a pool of equal amounts of individual RNA samples without RNA amplification.
Publication Title
RNA-Seq analysis of enteroendocrine cells reveals a role for FABP5 in the control of GIP secretion.
Sample Metadata Fields
No sample metadata fields
View Samples- Triticum aestivum
- 77 Downloadable Samples
- Affymetrix Wheat Genome Array (wheat)
Description
The use of statistical tools established for the genetic analysis of quantitative traits can be applied to gene expression data. Quantitative trait loci (QTL) analysis can associate expression of genes or groups of genes with particular genomic regions and thereby identify regions that play a role in the regulation of gene expression. A segregating population of 41 doubled haploid (DH) lines from the hard red spring wheat cross RL4452 x AC Domain was used. This population had previously been mapped with microsatellites and includes a full QTL analysis for agronomic and seed quality traits. Expression analysis from 5 day post anthesis developing seed was conducted on 39 of the 41 DH lines using the Affymetrix wheat array. Expression analysis of developing seeds from field grown material identified 1,327 sequences represented by Affymetrix probe sets whose expression varied significantly between genotypes of the population. A sub-set of 378 transcripts were identified that each mapped to a single chromosome interval illustrating that major expression QTLs can be found in wheat. Genomic regions corresponding to multiple expression QTLs were identified that were coincident with previous identified seed quality trait QTL. These regions may be important regulatory regions governing economically important traits. Comparison of expression mapping data with physical mapping for a sub-set of sequences showed that both cis and trans acting expression QTLs were present.
Publication Title
Identifying regions of the wheat genome controlling seed development by mapping expression quantitative trait loci.
Sample Metadata Fields
No sample metadata fields
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