To investigate the impact of the iNKT cells on the tumor-infiltrating leukocytes in TRAMP mouse prostate cancer.
Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression.
Age, Specimen part
View SamplesAcute myeloid leukemia (AML) is a complex, heterogeneous disease with variable outcomes following curative intent chemotherapy. AML with inv(3) is a genetic subgroup characterized by low response rate to induction type chemotherapy and hence is among the worst long term survivorship of the AMLs. Here, we present RNA-Seq transcriptome data from OCI-AML-20, a new AML cell line with inv(3) and deletion of chromosome 7. Overall design: RNA-Seq transcriptome analysis of OCI-AML-20 cell line with three biological replicates.
Characterization of inv(3) cell line OCI-AML-20 with stroma-dependent CD34 expression.
Disease, Cell line, Subject
View SamplesCooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. Highly activated SYK is predominantly found in FLT3-ITD positive AML and cooperates with FLT3-ITD to activate MYC transcriptional programs. FLT3-ITD AML cells are more vulnerable to SYK suppression than FLT3 wild-type counterparts. In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative disease (MPD) development, and SYK overexpression promotes overt transformation to AML and resistance to FLT3-ITD-targeted therapy.
SYK is a critical regulator of FLT3 in acute myeloid leukemia.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesWe introduced the HCMV IE1 gene into a mouse model of spontaneous glioma driven by p53KD and overexpression of Ras and PDGF and compared the transcriptomes of mouse gliomas +/- IE1. The following plasmids were utilized for glioma induction in equal parts: pT2/C-Luc/PGK-SB100, pT2/Cag-NrasV12, pT2/shP53/GFP4/mPDGF, and pT2/Cag-IE1 or pT2/C-Neo.
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesPrimary human GBM stem like cells were infected with HCMV TR strain (MOI=1) and treated with IE siRNA (a combination of oligos targeting IE1 and IE2 HCMV genes)
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesEnvironmental factors shape the phenotypes of multicellular organisms. The production of stomata—the epidermal pores required for gas exchange in plants—is highly plastic, and provides a powerful platform to address environmental influence on cell differentiation [1-3]. Rising temperatures are already impacting plant growth, a trend expected to worsen in the near future [4]. High temperature inhibits stomatal production but the underlying mechanism is not known [5]. Here, we show that elevated temperature suppresses the expression of SPEECHLESS (SPCH), the bHLH transcription factor that serves as the master regulator of stomatal lineage initiation [6,7]. Our genetic and expression analyses indicate that the suppression of SPCH and stomatal production is mediated by the bHLH transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), a core component of high temperature signaling [8]. Importantly, we demonstrate that upon exposure to high temperature, PIF4 accumulates in the stomatal precursors and binds to the promoter of SPCH. In addition, we find SPCH feeds back negatively to the PIF4 gene. We propose a model where the high temperature-activated PIF4 binds and represses SPCH expression to restrict stomatal production at high temperature. Our work identifies a molecular link connecting high temperature signaling and stomatal development, and reveals a direct mechanism by which production of a specific cell lineage can be controlled by a broadly-expressed environmental signaling factor. Overall design: Gene expression profiles following 12 hr Dex-induction of control and ML1p:SPCH1-4A-expressing Arabidopsis plants grown in liquid culture. Four replicates per line at 0 and 12 hr.
Direct Control of SPEECHLESS by PIF4 in the High-Temperature Response of Stomatal Development.
Age, Subject
View SamplesInfertility in lactating dairy cows is explained partially by the metabolic state associated with high milk production. The hypothesis was that lactating and non-lactating cows would differ in endometrial and placental transcriptomes during early pregnancy (day 28 to 42) and this difference would explain the predisposition for lactating cows to have embryonic loss at that time. Cows were either milked or not milked after calving. Reproductive [endometrium (caruncular and intercarunclar) and placenta] and liver tissues were collected on day 28, 35, and 42 of pregnancy. The primary hypothesis was rejected because no effect of lactation on mRNA abundance within reproductive tissues was found. Large differences within liver demonstrated the utility of the model to test an effect of lactation on tissue gene expression. Major changes in gene expression in reproductive tissues across time were found. Greater activation of the transcriptome for the recruitment and activation of macrophages was found in the endometrium and placenta. Changes in glucose metabolism between day 28 and 42 included greater mRNA abundance of rate-limiting genes for gluconeogenesis in intercaruncular endometrium and evidence for the establishment of aerobic glycolysis (Warburg effect) in the placenta. Temporal changes were predicted to be controlled by CSF1, PDGFB, and JUN. Production of nitric oxide and reactive oxygen species by macrophages was a mechanism to promote angiogenesis in the endometrium. Reported differences in pregnancy development for lactating versus non-lactating cows could be explained by systemic glucose availability to the conceptus and appear to be independent of the endometrial and placental transcriptomes.
The transcriptome of the endometrium and placenta is associated with pregnancy development but not lactation status in dairy cows.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNA methylation profiling reveals a predominant immune component in breast cancers.
Specimen part, Disease stage, Cell line, Treatment
View SamplesBreast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known expression subtypes but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients.
DNA methylation profiling reveals a predominant immune component in breast cancers.
Disease stage
View Samples