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GSE10113
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study aimed at exploring the physiological function of mammalian HYPB by means of knockout mouse model. Homogenous disruption of mouse Hypb gene leads to embryonic lethality at E10.5-E11.5. Severe vascular defects were observed in the Hypb-/- embryos, yolk sac and placenta.In the mutant embryo and yolk sac, disorganized and abnormally dilated capillaries cannot be remodeled into large blood vessels or intricate networks. Thus, our results suggest that the mammalian HYPB HMT plays an important role in embryonic vascularization.
Publication Title
Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The differentiation of leukemia stem cells (LSCs) is generally regarded as a one-way alterative process to self-renewal. However, how differentiation impacts LSC stemness has largely been unexplored. Here we show that before reaching terminal differentiation (TD), apical LSCs of mouse acute promyelocytic leukemia passed through a partial differentiation (PD) stage, wherein the leukemia cells re-initiated leukemia via de-differentiation albeit at a reduced rate. Notably, while retinoic acid (RA) preferentially drove the transition of LSC to PD, monocytic Irf8 skewed PD cells to terminal maturation over de-differentiation and/or expansion. Remarkably, the combined use of RA and Irf8 induction depleted the total leukemogenic potential, which indicates that discrete stage- or lineage-specific mechanisms elaborate a step-wise LSC differentiation.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To understand the biological function of GSTT1 deletion in diffuse large B cell lymphoma (DLBCL), we identified genes that are expressed differently in lymph node tissues from DLBCL patients collected at diagnosis with GSTT1 deletion (4 cases) compared to those without GSTT1 deletion (4 cases).
Publication Title
GSTT1 deletion is related to polycyclic aromatic hydrocarbons-induced DNA damage and lymphoma progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The high concentration of Well5 cells was resuspended into 20l PBS, the needle along the tibia direction, before reaching in a breakthrough sense, direct injection cells. At 7 days after injection, proximal tibia was able to reach mass production. At 20 days after injection, the proximal tibia mass increased.If prolonging exposure by BLI,this stage displayedthat tumor cell signalsbegan to lung metastasis. Osteosarcoma orthotopic lung metastasis model was successfully constructed. Total RNA was extracted from sorted osteosarcoma cells of the primary site and lung metastases using Trizol (Invitrogen).
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
SETD2/HYPB has been known as a histone H3K36 specific methyltransferase. However, its roles in physiology such as development and cellular function remain unclear. In this study, using mESCs as cellular model, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) towards primitive endoderm. This study aimed at exploring how did Setd2 regulate primitive endoderm. differentiation.
Publication Title
H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block the RAS oncogenic signaling by a distinct mechanism. Since the biological activity of RAS proteins rely upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors. Further analyses show that NADA is more active in inhibiting the NRAS transformation and signaling than that of KRAS4B. Mechanistically, NADA blocks the plasma membrane translocation of NRAS, but not that of KRAS4B. In addition, NADA inhibits the plasma membrane translocation and neoplastic transformation of oncogenic KRAS4A. Interestingly, NADA also redistributes the cytoplasmic NRAS to the Golgi apparatus in a palmitoylation-dependent manner. The results indicate that NADA inhibits NRAS and KRAS4A plasma membrane translocation by targeting a novel molecular process. The new findings would help to develop novel targeted therapies for a broad range of human cancers.
Publication Title
N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hairy cell leukemia (HCL) shows unique clinico-pathological and biological features. HCL responds well to purine analogues but relapses are frequent and novel therapies are required. BRAF-V600E is the key driver mutation in HCL and distinguishes it from other B-cell lymphomas, including HCL-like leukemias/lymphomas (HCL-variant and splenic marginal zone lymphoma). The kinase-activating BRAF-V600E mutation also represents an ideal therapeutic target in HCL. Here, we investigated the biological and therapeutic importance of the activated BRAF-MEK-ERK pathway in HCL by exposing in vitro primary leukemic cells purified from 26 patients to clinically available BRAF (Vemurafenib; Dabrafenib) or MEK (Trametinib) inhibitors. Results were validated in vivo in samples from Vemurafenib-treated HCL patients within a phase-2 clinical trial. BRAF and MEK inhibitors caused, specifically in HCL (but not HCL-like) cells, marked MEK/ERK dephosphorylation, silencing of the BRAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression signature, downregulation of the HCL markers CD25, TRAP and cyclin-D1, smoothening of leukemic cells' hairy surface, and, eventually, apoptosis. Apoptosis was partially blunted by co-culture with bone marrow stromal cells antagonizing MEK-ERK dephosphorylation. This protective effect could be counteracted by combined BRAF and MEK inhibition. Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.
Publication Title
BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We used microarrays to evaluate the global programme of gene expression after Dox inducible Yamanaka factors ectopic expression and identified distinct classes of genes during this biological process in vivo.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To investigate the molecular basis for the reversible suppression of HSCs by leukemia, we sorted the CD45.1+LKS+ population from control or leukemic mice at day 7 and day 14 for gene expression profiling analysis.
Publication Title
Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Time
View Samples