H929 human myeloma cells were exposed to aminopeptidase inhibitor (CHR-2797), HDAC inhibitor (CHR-3996), or a combinaion of the two agents, for 24 hours.
The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway.
Specimen part, Cell line, Treatment
View SamplesNeonates often generate incomplete immunity against intracellular pathogens, although the mechanism of this defect is poorly understood. An important question is whether the impaired development of memory CD8+ T cells in neonates is due to an immature priming environment or lymphocyte-intrinsic defects. Here we show that neonatal and adult CD8+ T cells adopted different fates when responding to equal amounts of stimulation in the same host. While adult CD8+ T cells differentiated into a heterogeneous pool of effector and memory cells, neonatal CD8+ T cells preferentially gave rise to short-lived effector cells and exhibited a distinct gene expression profile. Surprisingly, impaired neonatal memory formation was not due to a lack of responsiveness, but instead because neonatal CD8+ T cells expanded more rapidly than adult cells and quickly became terminally differentiated. Collectively, these findings demonstrate that neonatal CD8+ T cells exhibit an imbalance in effector and memory CD8+ T cell differentiation, which impairs the formation of memory CD8+ T cells in early life Overall design: mRNA profiles of effector CD8+ T cells from neonatal and adult mice
Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life.
No sample metadata fields
View SamplesWe stratified colorectal tumor samples using a new unsupervised, iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes.
Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines.
Sex, Race
View SamplesDuring immune ontogeny the thymus is colonized by distinct waves of hematopoietic stem cells that give rise to unique lineages of immune cells. In this report, we asked whether the developmental origin of CD8+ T cells influences their response to infection later in adulthood. To answer this question, we developed a system to 'timestamp' CD8+ T cells in situ at various stages of development (1d and 28d) and examined their behavior at 8 weeks of age. We found that neonatal-derived CD8+ T cells have an intrinsic propensity to become memory phenotype cells prior to infection and are the first cells to proliferate and become effectors after microbial challenge. These data indicate that there are developmental layers in the adult CD8+ T cell response to infection and that the heterogeneity in the effector pool is linked to the variation in the developmental origins of the responding cells. This dataset profiles gene expression in 1day- and 28day-timestamped naïve CD8+ T cells in 8 week old mice. Overall design: gene expression profiling of naïve CD8+ T cells in 8 week old mice, looking at two samples: cells made at 1 day or 28 days of life, in duplicate.
Developmental Origin Governs CD8<sup>+</sup> T Cell Fate Decisions during Infection.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Specimen part, Subject
View SamplesT lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells.
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Specimen part
View SamplesT lymphocytes are conventionally divided into subsets based upon expression of co-receptors, cytokines and surface molecules. By mRNA microarray analysis, T lymphocytes that express the C-type lectin CD161 were identified to share a transcriptional profile, which led to the identification of an innate function across these previously defined subsets, including CD8, CD4 and TCRgd T cells.
CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.
Specimen part
View SamplesWe report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells. Overall design: hiPSC-CMs from 3 affected (Left Ventricular Hypertrophy [LVH]) and 3 non-affected donors were sequenced using ThermoFisher's whole transcriptome targeted AmpliSeq assay
A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling.
Specimen part, Disease, Subject
View SamplesAnalysis of aldosterone-producing adenoma (APA) samples from patients with primary hyperaldosteronism. These APAs have a somatic mutation in either KCNJ5, CACNA1D, or ATP1A1. Results provide insight into the different mechanisms each mutation may cause leading to elevated aldosterone production in APA.
Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension.
Specimen part, Disease, Disease stage
View SamplesTRF2 is a paralogue of TATA-box binding protein (TBP) with highest expression in testis. Although Trf2 inactivation in mice leads to arrested spermatogenesis, there is no direct evidence that Trf2 is recruited to chromatin to directly regulate gene expression. We used genetically modified mice where endogenous Trf2 has been modified to carry a TAP-TAG to perform ChIP-reChIP followed by deep sequencing. We found that Trf2 is recruited to all active promoters as a subunit of TFIIA/ALF complex together with TBP. To assess the effect of Trf2 inactivation on gene expression we performed RNA-seq on WT and Trf2-/- testes at 21 days of age when haploid cell gene expression is activated. Overall design: The testes from three 21 day old WT and three Trf2-/- males were taken to prepare total RNAs for deep sequencing.
TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression.
Specimen part, Subject
View Samples