CD4+ T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes, resulting from CD4+ T-cell help during priming, as apparent in effector CTLs. This gene expression signature reveals that CD4+ T-cell help optimizes CTLs in the expression of cytotoxic effector molecules, but also in many other functions that ensure optimal efficacy of CTLs throughout their life cycle. Overall design: Whole transcriptome analysis of effector CD8 T cells primed in the presence or absence of CD4 T cell help after vaccination or virus infection, or treated with agonistic CD27 or blocking CD70 antibody after vaccination.
CD4<sup>+</sup> T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness.
Specimen part, Cell line, Subject
View SamplesAcross life neural stem cells (NSCs) generate new neurons in the mammalian brain through asymmetric neurogenic and self-renewing cell divisions. However, the cellular mechanisms underlying NSC asymmetry remain unknown. Using fluorescence loss in photobleaching (FLIP) we here show that NSCs in vitro and within the developing forebrain generate a lateral diffusion barrier during cell division resulting in asymmetric segregation of cellular components. The strength of the diffusion barrier is dynamically regulated with age and depends on the proper function of lamin-associated nuclear envelope constituents. Strikingly, age-associated or experimental impairment of the diffusion barrier disrupts asymmetric segregation of damaged proteins, a product of aging. Thus, the data presented here identify a mechanism how age is asymmetrically distributed during somatic stem cell division.
A mechanism for the segregation of age in mammalian neural stem cells.
Age, Specimen part
View SamplesA fundamental issue in cell biology is how migratory cell behaviors are controlled by dynamically regulated cell adhesion.
Ovo1 links Wnt signaling with N-cadherin localization during neural crest migration.
Age, Specimen part
View SamplesCells constantly adapt to changes in their environment. In the majority of cases, the environment shifts between conditions that were previously encountered during the course of evolution, thus enabling evolutionary-programmed responses. In rare cases, however, cells may encounter a new environment to which a novel response is required. To characterize the first steps in adaptation to a novel condition, we studied budding yeast growth on xylulose, a sugar that is very rarely found in the wild. We previously reported that growth on xylulose induces the expression of amino-acid biosynthesis genes, in multiple natural yeast isolates. This induction occurs despite the presence of amino acids in the growth medium and is a unique response to xylulose, not triggered by any of the naturally available carbon sources tested. Propagating these strains for ~300 generations on xylulose significantly improved their growth rate. Notably, the most significant change in gene expression was the loss of amino acid biosynthesis gene induction. Furthermore, the reduction in amino-acid biosynthesis gene expression on xylulose was strongly correlated with the improvement in growth rate, suggesting that internal depletion of amino-acids presented the major bottleneck limiting growth in xylulose. We discuss the possible implications of our results for explaining how cells maintain the balance between supply and demand of amino acids during growth in evolutionary 'familiar' vs. 'novel' conditions. Overall design: mRNA profiles of 12 wt S. cerevisiae strains grown on either YPD or YP-xylulose, before and after 300 generations evolution on YP-xylulose
Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source.
Cell line, Subject
View SamplesWe initiated a study to investigate the transcriptional profiles associated with cell states of the stomatal lineage. A stem-cell like precursor of stomata, a meristemoid. reiterates asymmetric divisions and renews itself before differentiating into guard cells. The transient and asynchronous nature of the meristemoid has made it difficult to study its molecular characteristics. Through combinatorial use of genetic resources that either arrest or constitutively drive stomatal cell-state progressions due to loss- or gain-of-function mutations in the key transcription factor genes, SPEECHLESS, MUTE, and SCRM, we obtained seedlings highly enriched in pavement cells, meristemoids, or stomata. Here we present transcriptome and genome-wide trends in gene regulation associated with each cell state and identify molecular signatures associated with meristemoids.
Molecular profiling of stomatal meristemoids reveals new component of asymmetric cell division and commonalities among stem cell populations in Arabidopsis.
Age, Specimen part
View SamplesSIN3 is a master transcriptional scaffold protein. SIN3 interacts with RPD3 and other accessory proteins to form a histone modifying complex. A single Sin3A gene encodes multiple isoforms of SIN3, of which SIN3 187 and SIN3 220 are the predominant isoforms. Previous studies demonstrated that SIN3 isoforms play non-redundant roles during fly development. In the current study, we sought to investigate the genes regulated by SIN3 187. Overall design: S2 cells and cells carrying a stable transgene of SIN3 187HA (SIN3 187HA cells) were treated with 0.07 µM CuSO4. CuSO4 treatment led to ectopic expression of SIN3 187HA. S2 cells were used as a control. Following induction, total mRNA was extracted. mRNA profiling of these samples were performed by deep sequencing using Illumina Hiseq2500. Three biological replicates were performed.
Genome-wide studies reveal novel and distinct biological pathways regulated by SIN3 isoforms.
Cell line, Subject
View SamplesFor each strain two time courses for mRNA abundance: Oxidative and MMS and two time courses for decay: reference decay and following oxidative stress
Transcriptome kinetics is governed by a genome-wide coupling of mRNA production and degradation: a role for RNA Pol II.
No sample metadata fields
View SamplesTransformation of Glycine max with seed-targeted expression vectors via Agrobacterium causes measurable unscripted gene expression changes in the seed transcriptome Overall design: mRNA was sequenced from three transgenic events expressing three different recombinant proteins in soybean seeds. Three plants were chosen from each as group replicates, and three seeds from each plant as individual biological replicates.
Transcript Polymorphism Rates in Soybean Seed Tissue Are Increased in a Single Transformant of <i>Glycine max</i>.
Subject
View SamplesClassic ‘position effect’ experiments repositioned genes to the telomere to demonstrate that the epigenetic landscape can dramatically alter gene expression. Here we show that systematic gene knockout collections provide an exceptional resource for interrogating position effects, not only at the telomere but at every single genetic locus. Because deleted genes are replaced by the same reporter gene, interrogation of this reporter provides a sensitive probe into many different chromatin environments while controlling for genetic context. Using this approach we find that, whereas replacement of yeast genes with the kanMX marker does not perturb the chromatin landscape, differences due to gene position account for more than 35% of marker gene activity. We observe chromatin influences different from those reported previously, including an antagonistic interaction between histone H3 lysine 36 trimethylation (H3K36me3) and the Rap1 transcriptional activation site in kanMX that is mediated through a Set2-Rpd3-dependent pathway. This interaction explains why some yeast genes have been resistant to deletion and allows successful generation of these deletion strains using a modified transformation procedure. These findings demonstrate that chromatin regulation is not governed by a uniform ‘histone code’, but by specific interactions between chromatin and genetic factors. Overall design: Data included are RNA-Seq data for 4 heterzygous diploid yeast strains and diploid wild-type. Therea re three replicates for each heterzygous strain, and six replicates for wild-type.
Decoupling epigenetic and genetic effects through systematic analysis of gene position.
Subject
View SamplesIn this study, using a Patient Derived Xenograft (PDX) system established by transplanting primary tumors from pre-metastatic breast cancer patients we demonstrate that development of distant organ metastases correlates with the presence of Bone Marrow Disseminated Tumor Cells (BM DTCs) in the PDX mice. Comparative gene expression analysis of bone marrow (BM) from tumor bearing PDX mice which developed metastatic disease was carried out with BM from non-tumor bearing controls.
Identifying biomarkers of breast cancer micrometastatic disease in bone marrow using a patient-derived xenograft mouse model.
Specimen part
View Samples