This SuperSeries is composed of the SubSeries listed below.
ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer.
Specimen part, Cell line, Treatment
View SamplesA significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. To model resistance to aromatase inhibitor (AI) therapy, long-term estrogen-deprived (LTED) derivatives of MCF-7 and HCC-1428 cells were generated through culture for 3 and 7 months under hormone-depleted conditions, respectively. These LTED cells showed sensitivity to the ER downregulator fulvestrant under hormone-depleted conditions, suggesting continued dependence upon ER signaling for hormone-independent growth. To evaluate the role of ER in hormone-independent growth, LTED cells were treated +/- 1 uM fulvestrant x 48 h before RNA was harvested for gene expression analysis.
ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer.
Specimen part, Cell line, Treatment
View SamplesRNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets, Affymetrix HG-U133Plus 2.0 arrays were hybridized with probe from total RNA isolated from blood sampled from 6 umbilical cords and 6 healthy adult humans.
Let-7 microRNAs are developmentally regulated in circulating human erythroid cells.
Specimen part
View SamplesHyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer.
Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer.
Specimen part, Cell line
View SamplesMultiple sclerosis involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system. Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells are stem cells in the central nervous system and the principal source of myelinating oligodendrocytes. These cells are abundant in demyelinated regions of patients with multiple sclerosis, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention. To discover therapeutic compounds for enhancing myelination from endogenous oligodendrocyte progenitor cells, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem-cell-derived oligodendrocyte progenitor cells. Here we show seven drugs function at nanomolar doses selectively to enhance the generation of mature oligodendrocytes from progenitor cells in vitro. Two drugs, miconazole and clobetasol, are effective in promoting precocious myelination in organotypic cerebellar slice cultures, and in vivo in early postnatal mouse pups. Systemic delivery of each of the two drugs significantly increases the number of new oligodendrocytes and enhances remyelination in a lysolecithin-induced mouse model of focal demyelination. Administering each of the two drugs at the peak of disease in an experimental autoimmune encephalomyelitis mouse model of chronic progressive multiple sclerosis results in striking reversal of disease severity. Immune response assays show that miconazole functions directly as a remyelinating drug with no effect on the immune system, whereas clobetasol is a potent immunosuppressant as well as a remyelinating agent. Mechanistic studies show that miconazole and clobetasol function in oligodendrocyte progenitor cells through mitogen-activated protein kinase and glucocorticoid receptor signalling, respectively. Furthermore, both drugs enhance the generation of human oligodendrocytes from human oligodendrocyte progenitor cells in vitro. Collectively, our results provide a rationale for testing miconazole and clobetasol, or structurally modified derivatives, to enhance remyelination in patients. Overall design: RNA sequencing of oligodendrocyte progenitor cells treated with vehicle, miconazole or clobetasol for 0, 2, 6, or 12 hours. Cells were plated 1.5 hours prior to addition of drug.
Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo.
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View SamplesA significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation.
A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer.
Cell line, Treatment
View SamplesMicroarray analysis of the changes in transcript abundance in cell culture and shoot
Heterogeneity of the mitochondrial proteome for photosynthetic and non-photosynthetic Arabidopsis metabolism.
Specimen part
View SamplesIn Caenorhabditis elegans, the six proteins that make up the REF-1 family are HES homologs that act in both Notch dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the REF-1 family works to coordinate post-embryonic cellular events, we performed transcriptome analysis of HLH-25 and HLH-29 mutant strains.
Genome-wide microarrray analysis reveals roles for the REF-1 family member HLH-29 in ferritin synthesis and peroxide stress response.
Sex, Specimen part
View SamplesThe circadian clock generates biological rhythms with a period of approximately 24 hours. Using microarray experiments, we have previously shown that approximately 16% of the Arabidopsis genome is regulated in a circadian manner (Edwards et al., 2006). Previous work from our lab in modelling the molecular oscillator of Arabidopsis introduced a hypothetical component Y into an evening loop of the clock gene network (Locke et al., 2005). GIGANTEA (GI) was suggested as a strong candidate for Y based on genetic evidence and its close matching of the expression profile predicted by the mathematical modelling. Recent experimental evidence suggests that GI may only partially account for the function of Y. Thus, we are undertaking a genomics approach to identify other candidate genes that match the predicted expression profile of Y. Samples were taken from wild type and lhy cca1 double mutant seedlings from 4 timepoints around the night to day transition (-15mins, +15mins, +30mins and +60mins) after 9 days of growth in 18:6 light dark cycles. We aim to identify genes showing the light induction response predicted for Y around dawn.
The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops.
Specimen part, Time
View SamplesTranscript abundance profiles were examined over the first 24 hours of germination in rice grown under aerobic conditions.
Experimental analysis of the rice mitochondrial proteome, its biogenesis, and heterogeneity.
Specimen part, Time
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