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GSE40155
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Mutations of RUNX1 are detected in patients with myelodysplastic syndrome (MDS). In particular, C-terminal truncation mutations lack a transcription regulatory domain and have increased DNA binding through the runt homology domain (RHD). The expression of the RHD, RUNX1(41-214), in mouse hematopoietic cells induced progression to MDS and acute myeloid leukemia (AML). Analysis of pre-myelodysplastic animals revealed expansion of c-Kit+Sca-1+Lin- (KSL) cells and skewed differentiation to myeloid at the expense of the lymphoid lineage. These abnormalities correlate with the phenotype of Runx1-deficient animals, as expected given the reported dominant-negative role of C-terminal mutations over the full-length RUNX1. However, MDS is not observed in Runx1-deficient animals. Gene expression profiling revealed that RUNX1(41-214) KSLs have an overlapping yet distinct gene expression profile from Runx1-deficient animals. Moreover, an unexpected parallel was observed between the hematopoietic phenotype of RUNX1(41-214) and aged animals. Genes deregulated in RUNX1(41-214), but not in Runx1-deficient animals, were inversely correlated with the aging gene signature of hematopoietic stem cells (HSC), suggesting that disruption of the expression of genes related to normal aging by RUNX1 mutations contributes to development of MDS. The data presented here provide insights into the mechanisms of development of MDS in HSCs by C-terminal mutations of RUNX1.
Publication Title
Expression of the runt homology domain of RUNX1 disrupts homeostasis of hematopoietic stem cells and induces progression to myelodysplastic syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
High levels of Hes1 expression are frequently found in BCR-ABL-positive chronic myelogenous leukemia in blast crisis (CML-BC). In mouse bone marrow transplantation (BMT) models, co-expression of BCR-ABL and Hes1 induces CML-BClike disease; however the underlying mechanism remained elusive. Here, based on gene expression analysis, we show that MMP-9 is upregulated by Hes1 in common myeloid progenitors (CMPs). Analysis of promoter activity demonstrated that Hes1 upregulated MMP-9 by activating NF-kB. Analysis of 20 samples from CML-BC patients showed that MMP-9 was highly expressed in three, with two exhibiting high levels of Hes1 expression. Interestingly, MMP-9 deficiency impaired the cobblestone area-forming ability of CMPs expressing BCR-ABL and Hes1 that were in conjunction with a stromal cell layer. In addition, these CMPs secreted MMP-9, promoting the release of soluble Kit-ligand (sKitL) from stromal cells, thereby enhancing proliferation of the leukemic cells. In accordance, mice transplanted with CMPs expressing BCR-ABL and Hes1 exhibited high levels of sKitL as well as MMP-9 in the serum. Importantly, MMP-9 deficiency impaired the development of CML-BClike disease induced by BCR-ABL and Hes1 in mouse BMT models. The present results suggest that Hes1 promotes the development of CML-BC, partly through MMP-9 upregulation in leukemic cells.
Publication Title
Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
BRAF inhibitors are highly effective therapies for patients with BRAF V600 mutated metastatic melanoma. Patients who receive BRAF inhibitors develop a variety of hyper-proliferative skin conditions, whose pathogenic basis is the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyper-proliferative skin changes improve when a MEK inhibitor is co-administered, as a MEK inhibitor blocks paradoxical MAPK activation. We tested whether we could take advantage of the mechanistic understanding of the skin hyper-proliferative side effects of BRAF inhibitors to accelerate skin wound healing by inducing paradoxical MAPK activation. Here we show that the BRAF inhibitor vemurafenib accelerates human keratinocyte proliferation and migration by increasing ERK phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing models in mice accelerated cutaneous wound healing and improved the tensile strength of healing wounds through paradoxical MAPK activation; addition of a MEK inhibitor reversed the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor did not increase the incidence of cutaneous squamous cell carcinomas in mice even after the application of a carcinogen. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds. Overall design: Full depth incisional wound mice tissues with/without Vemurafenib treatment were sent for RNAseq analysis on day 2, 6 and 14
Publication Title
Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used the myoma model in conjunction with gene expression profiling with microarray data as an efficient tool for high throughput analysis and to screen for differentially expressed genes. Our aim was to identify candidates playing an important role in SLPI and/or MMP-promoted tumor invasion by comparing oral carcinoma Ca9-22 cells, which highly express secretory leukocyte protease inhibitor (SLPI) gene, with SLPI-deficient Ca9-22 cells.
Publication Title
Human uterus myoma and gene expression profiling: A novel in vitro model for studying secretory leukocyte protease inhibitor-mediated tumor invasion.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 1500
Description
Despite the importance of memory B cells for protection from recurrent infection, how these cells are selected during germinal center (GC) reactions remains unclear. We show here that light zone (LZ) GC B cells with lower affinity BCRs express a less CD40 signature and relatively high levels of Bach2, being prone to enter the memory B cell pool. We also find that Bach2 contributes to memory B cell generation in a Blimp-1 independent manner and that its higher expression confers on LZ GC cells a more advantage for entering the memory B cell compartment. Thus, our data support an instructive model in which weak T cell help keeps Bach2 expression relatively high, thereby being predisposed to enter the memory pool. Overall design: mRNA expression profiles of NP specific high and low affinity IgG1 LZ GC B cells were generated by deep sequencing using Illumina HiSeq 1500
Publication Title
Regulated selection of germinal-center cells into the memory B cell compartment.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 1500
Description
Despite the importance of memory B cells for protection from recurrent infection, how these cells are selected during germinal center (GC) reactions remains unclear. We show here that light zone (LZ) GC B cells with lower affinity BCRs express a less CD40 signature and relatively high levels of Bach2, being prone to enter the memory B cell pool. We also find that Bach2 contributes to memory B cell generation in a Blimp-1-independent manner and that its higher expression confers on LZ GC cells a more advantage for entering the memory B cell compartment. Thus, our data support an instructive model in which weak T cell help keep Bach2 expression relatively high, thereby being predisposed to enter the memory pool. Overall design: mRNA expression profiles of Bach2-tdRFP low and high expression NP-specific IgG1 light zone GC B cells were generated by deep sequencing using Illumina HiSeq 1500.
Publication Title
Regulated selection of germinal-center cells into the memory B cell compartment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
From comprehensive expression analysis of RNAseq data, IGF2R was found to correlate with poor prognosis in cervical cancer. Gene knockdown of IGF2R lead to cell death in cervical cancer. To reveal its biological function, we performed microarray analysis using IGF2R knockdown cervical cancer cells.
Publication Title
Upregulation of IGF2R evades lysosomal dysfunction-induced apoptosis of cervical cancer cells via transport of cathepsins.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Alveolar macrophages (AMs) of Bach2 KO mice show multiple alternations in their functions including lipid metabolism. We aimed to clarify the mechanism whereby deficiency of Bach2 impairs the function of AMs and ruins the homeostasis of lungs. Now we report that some cytokines produced from Bach2-deficient T cells alter the character of AMs and expression of Bach2 is necessary for AMs to maintain the function of lipid metabolism. Overall design: mRNA profiling of AMs from 16-week old control mice, Bach2-floxed CD4cre mice, WT mice and Bach2 germline KO mice were examined by deep sequencing using HiSeq2500. Please note that two macrophage populations observed in Bach2-floxed/CD4-cre cKO mice were analyzed; One with normal surface marker phenotype that was the same as control mice (normal). The other with aberrant surface marker phenotype compared with control mice (abnormal).
Publication Title
Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Nardilysin (NRDc), a metalloendopeptidase of the M16 family, has been reported to promote the ectodomain shedding and resulting activation of various growth factors and cytokines, but its role in cancer biology have not been elucidated.
Publication Title
Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-α.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 256 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify the specific genes for subtyping.
Publication Title
Discovery of a Good Responder Subtype of Esophageal Squamous Cell Carcinoma with Cytotoxic T-Lymphocyte Signatures Activated by Chemoradiotherapy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples