This SuperSeries is composed of the SubSeries listed below.
An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia.
Specimen part, Cell line
View SamplesHere we modeled T-ALL resistance to Notch inhibition, identifying persister cells that readily expand in the presence of gamma secretase inhibitor (GSI) and the absence of Notch signaling. Rare persister cells are already present in nave T-ALL populations, and the reversibility of the phenotype is suggestive of an epigenetic mechanism. Relative to GSI-sensitive cells, persisters activate distinct signaling and gene expression programs, and exhibit global chromatin compaction. A shRNA screen identified chromatin regulators whose depletion preferentially impairs persister cell viability, including BRD4, an acetyl-histone reader. BRD4 is up-regulated in the persisters and binds enhancers near genes with critical functions in T-ALL, including MYC and BCL2. Treatment of persisters with the BRD4 inhibitor JQ1 down-regulates these targets and induces growth arrest and apoptosis, at doses well tolerated by GSI-sensitive cells. Prompted by these findings, we examined and established the efficacy of GSI JQ1 combination therapy against primary human leukemias in vivo. Our findings establish a role for epigenetic heterogeneity in leukemia drug resistance and suggest the potential of combination therapies that include epigenetic modulators to prevent and treat resistant disease.
An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia.
Specimen part, Cell line
View SamplesWe used microarrays to assess transcriptional changes in regulatory T cells upon deletion of PTEN.
No associated publication
Sex, Age
View SamplesThe goal of this experiment was to explore the extent of KIN10 (At3g01090) transcriptional regulation and identify its early target genes in Arabidopsis mesophyll protoplasts. Results suggest that KIN10 targets a remarkably broad array of genes that orchestrate transcription networks, promote catabolism and autophagy, and suppress anabolism and ribosome biogenesis. The transient expression condition ruled out secondary or long-term effects of metabolism and growth, and circumvented experimental limitations caused by redundancy and embryonic lethality observed in mammals and plants.
A central integrator of transcription networks in plant stress and energy signalling.
No sample metadata fields
View SamplesThe goal of this experiment was to investigate the early transcript changes (6h) induced by hypoxia treatment in mesophyll protoplasts. A single pair (control & hypoxia) of GeneChips was used to confirm that hypoxia treatment altered the expression of an overlapping set of genes controlled by KIN10 (At3g01090) in Arabidopsis mesophyll protoplasts.
A central integrator of transcription networks in plant stress and energy signalling.
No sample metadata fields
View SamplesEarly stages of host microbe adaptations involve 'system status changes' (rewiring of pre-existing cellular signaling networks and components) of the host and microbe. We posited that under certain environmental conditions these changes leads to maladaptations and favor emergence of new infectious diseases, and these adaptations will have characteristic signatures representative of the adaptation.
No associated publication
Specimen part
View SamplesComparison of gene expression in tumors grown in the brains and mammary fat pads of immunodeficient mice.
No associated publication
No sample metadata fields
View SamplesBackground: Central nervous system (CNS) metastases represent a major problem in the treatment of HER2-positive breast cancer due to the disappointing efficacy of HER2-targeted therapies in the brain microenvironment. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in preclinical models of brain metastases.
Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment.
Specimen part, Disease, Time
View SamplesWe performed gene expression microarray comparing Osx-mCherry cells and Ocn-Topaz cells isolated from the OsxCre-mCherry;OcnCre-Topaz double transgenic mice by flow cytometry.
Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow.
Specimen part
View SamplesComparative analysis of FACS-sorted CCR2- and CCR2+ HSC in the steady state. CCR2+ HSC have fourfold higher proliferative rates than CCR2- HSC, are are biased towards the myeloid lineage and dominate the migratory HSC population.
Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells.
Specimen part
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