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GSE37430
Homo sapiens
3 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5+ B lymphocytes in peripheral blood, lymphoid organs and BM. The main feature of the disease is accumulation of the malignant cells due to decreased apoptosis. CD84 belongs to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors, and has an unknown function in CLL cells. Here, we show that the expression of CD84 is significantly elevated from the early stages of the disease, and is regulated by macrophage migration inhibitory factor (MIF) and its receptor, CD74. Activation of cell surface CD84 initiates a signaling cascade that enhances CLL cell survival. Both immune-mediated neutralization or blockade of CD84 induce cell death in vitro and in vivo. In addition, analysis of samples derived from an on-going clinical trial, in which human subjects were treated with humanized anti-CD74 milatuzumab shows a decrease in CD84 mRNA levels milatuzumab-treated cells. This downregulation was correlated with reduction of Bcl-2 and Mcl-1 message. Thus, our data show that overexpression of CD84 in CLL is an important survival mechanism that appears to be an early event in the pathogenesis of the disease. These findings suggest novel therapeutic strategies based on the blockade of this CD84-dependent survival pathway.
Publication Title
CD84 is a survival receptor for CLL cells.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 1000
Description
Minocycline is a potent modulator of retinal microglia Overall design: Global mRNA expression analysis of CD1 mouse retinas in control, light damage and light damage plus minocycline conditions
Publication Title
Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dendritic cells (DCs) are crucial for sensing pathogens and triggering immune response. GM-CSF myeloid dendritic cells (GM-DCs) secrete several cytokines including IL-2 upon activation by pathogen associated molecular pattern (PAMP) ligands. DC IL-2 has been shown to be important for innate and adaptive immune responses, however its importance in DC physiology has never been demonstrated. This is due to ambiguity in expression of the CD122 subunit of the IL-2 trimeric receptor complex crucial for signaling. We show here that autocrine IL-2 signaling is functional in GM-DCs in early time window of stimulation with PAMPs. IL-2 signaling selectively activates the JAK/STAT5 pathway by assembling holo-receptor complexs at the cell surface. Autocrine IL-2 signaling inhibits survival of PAMP matured GM-DCs which is crucial for maintaining immune tolerance and preventing autoimmunity. Our findings suggest immune regulation by a novel autocrine signaling pathway that can potentially be exploited in DC immunotherapy.
Publication Title
Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A unique H2A histone variant occupies the transcriptional start site of active genes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Chromatin performs numerous functions during cellular differentiation, and therefore it must be capable of adopting a multitude of different structures. How these various structures are established is poorly understood, but we propose that specific histone H2A variants will have a key role in remodelling chromatin during differentiation. Structurally, we show here that the gain of just a single acidic amino acid residue has generated a new mouse H2A.Bbd-like histone variant, H2A.Lap1, and that when incorporated into nucleosomal arrays imparts on them unique biophysical properties that are distinct from arrays containing either H2A or human H2A.Bbd. Functionally, we identify H2A.Lap1 as a novel chromatin component of active genes that are expressed during spermatogenesis, and in combination with H2A.Z create a unique chromatin landscape at the start site of transcription. During round spermatid differentiation, H2A.Lap1 dramatically loads onto the inactive X chromosome enabling a subset of its genes to be transcriptionally activated.
Publication Title
A unique H2A histone variant occupies the transcriptional start site of active genes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We discover drugs with a dual-inhibitory mechanism provides a unique pharmacological strategy against cancer and evidence of cross-activation between the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways via a RasPIK3IP1PI3K signaling network
Publication Title
Dual blockade of the lipid kinase PIP4Ks and mitotic pathways leads to cancer-selective lethality.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
While it has been clearly established that well positioned H2A.Z-containing nucleosomes flank the nucleosome depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes 1,2, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in trophoblast stem (TS) cells, the level of H2A.Z at promoters decreases during S phase coinciding with homotypic (H2A.Z/H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z/H2A). Surprisingly, these nucleosomes remain heterotypic at M phase. At the TSS, we identify an unstable heterotypic H2A.Z-containing nucleosome in G1 which, strikingly, is lost following DNA replication. These dynamic changes in H2A.Z at the TSS mirror a global expansion of the NDR at S and M which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of H2A.Z at promoters, it is targeted to the centromere when mitosis begins.
Publication Title
Histone H2A.Z inheritance during the cell cycle and its impact on promoter organization and dynamics.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
CD34+ human cord blood-derived cells were subjected to GFP mRNA delivery or mock treatment using Centrifugation enhanced Nanostraw Transfection (CeNT) or conventional electroporation.
Publication Title
Efficient and nontoxic biomolecule delivery to primary human hematopoietic stem cells using nanostraws.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in glioma stem cells (GSCs) in individual HGG subtypes is poorly characterized. Here we identified and characterized two mutually exclusive GSC subtypes with distinct dysregulated signaling pathways. Analysis of mRNA profiles distinguished proneural (PN) from mesenchymal (Mes) GSCs and revealed a pronounced correlation with the corresponding PN or Mes HGGs. Mes GSCs displayed more aggressive phenotypes in vitro and as intracranial xenografts in mice. Further, Mes GSCs were markedly resistant to radiation compared with PN GSCs. The glycolytic pathway, comprising aldehyde dehydrogenase (ALDH) family genes and in particular ALDH1A3, were enriched in Mes GSCs. Glycolytic activity and ALDH activity were significantly elevated in Mes GSCs but not in PN GSCs. Expression of ALDH1A3 was also increased in clinical HGG compared with low-grade glioma or normal brain tissue. Moreover, inhibition of ALDH1A3 attenuated the growth of Mes but not PN GSCs. Last, radiation treatment of PN GSCs up-regulated Mes-associated markers and downregulated PN-associated markers, whereas inhibition of ALDH1A3 attenuated an irradiation-induced gain of Mes identity in PN GSCs. Taken together, our data suggest that two subtypes of GSCs, harboring distinct metabolic signaling pathways, represent intertumoral glioma heterogeneity and highlight previously unidentified roles of ALDH1A3-associated signaling that promotes aberrant proliferation of Mes HGGs and GSCs. Inhibition of ALDH1A3- mediated pathways therefore might provide a promising therapeutic approach for a subset of HGGs with the Mes signature.
Publication Title
Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3.
Sample Metadata Fields
Specimen part
View Samples