This SuperSeries is composed of the SubSeries listed below.
MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state.
Sex, Specimen part
View SamplesWe address the molecular mechanisms through which MYC promotes loss of cell identity and acquisition of stem cell-like traits, favouring the onset of tumorigenesis, by performing gene expression profile analyses in a transition from WT IMEC, IMEC over-expressing MYC and mammospeheres formed from IMEC-MYC (named M2). We then investigated the global gene expression profile of the fraction of cells hyper-activating the WNT pathway in M2 spheres, compared to the ones with low activation
MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state.
Sex, Specimen part
View SamplesWhite adipose tissue is primary involved in the response to insulin after feeding, while brain is not directly sensitive to insulin levels.
eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription.
Specimen part
View SamplesLiver is primary involved in the response to insulin after feeding. Hepatocytes activates a tightly controlled genetic programme where specific sets of genes are modulates in response to insulin, for activation of the anabolic pathways.
eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription.
Specimen part
View SamplesFTY720/Fingolimod, an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. Here we show that FTY720 enters the nucleus where it is phosphorylated by sphingosine kinase 2 (SphK2) and nuclear FTY720-P that accumulates there, binds and inhibits class I histone deacetylases (HDACs) enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in various brain regions, including hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning leading to improvement of memory impairment independently of its immunosuppressive actions. Our data suggest that sphingosine-1-phosphate and SphK2 play specific roles in memory functions and that FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories.
Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory.
Sex, Age, Specimen part, Treatment
View SamplesThis 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 SamplesThirty to 60% of CD56dimCD16bright NK cells in healthy adults express CD57, which is not expressed on immature CD56bright NK cells or fetal and newborn NK cells. We hypothesized that CD57+ NK cells within the CD56dim mature NK cell subset are highly mature and might be terminally differentiated.
CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset.
Specimen part, Subject
View SamplesEML1 and EML3 were previously shown to be histone readers involved in plant-pathogen interactions. To learn more about the developmental function of EML1 and EML3, we generated eml1 eml3 double mutant and showed that it had specific seed developmental phenotypes, including a capability to develop seed without fertilization. Next, we analyzed the mRNA expression of genes in the eml1 eml3 double mutant and compared it to its wild type. Differentially expressed (DE) genes in the mutant were identified and compared with DE of the mutants known to be involved in regulating seed development and in fertilization-independent endosperm development. Our results suggest that some targets are shared between EML histone readers and known regulators of seed development, such as MEA. Auxin response seems to be affected in both types of mutants. However, unlike MEA, EML proteins regulate auxin responsive genes not only in the endosperm, but also in the embryo. This capability makes EML proteins very good candidates for engineering apomictic seeds. Overall design: 3 eml1,eml3 double mutant samples and 3 WT samples
Arabidopsis EMSY-like (EML) histone readers are necessary for post-fertilization seed development, but prevent fertilization-independent seed formation.
Specimen part, Subject
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