Physical exercise training is a known protective factor against cardiovascular morbidity and mortality. Nevertheless, the underlying specific molecular mechanisms still remain uncompletely explored. To identify molecular mechanisms by which exercise training induces this favorable phenotype a genomic approach was used in an animal model of mild exercise previously demonstrated by our group to induce cardioprotection.
Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection.
No sample metadata fields
View SamplesComparing global gene expression of neonatal and adult natural killer cells to determine if differences in gene expression suggest that different developmental pathways during hematopoiesis are followed in the fetal and adult mouse to produce mature natural killer cells.
Expression of rearranged TCRgamma genes in natural killer cells suggests a minor thymus-dependent pathway of lineage commitment.
Age, Specimen part
View SamplesRNA transcriptome difference between WT and SFR KO iNKT cells To understand how SLAM family receptors (SFRs) contribute to iNKT cell development, a mouse lacking all SFRs in addition to the ligand of 2B4, CD48, was generated, and the transcriptional profiles of thymic iNKT cells from wild-type and SFR KO mice were compared, using RNA sequencing. Overall design: Examine RNA expression in WT and SFR KO iNKT cells Thymocytes were isolated from WT and SFR KO mice, and iNKT cells were enriched by negative selection. Unwanted cells (CD11b+ CD11c+ Gr-1+ Ter-119+ CD19+ CD8a+ cells) were targeted for removal with biotinylated antibodies (BioLegend), streptavidin-coated magnetic particles (RapidSpheres) and EasySep magnet (STEMCELL), and followed by staining with mCD1d/PBS-57 and anti-TCR. Then, iNKT cells were sorted with BD FACSAria III (BD Biosciences), and total RNA was isolated from sorted cells according to the manufacturer's instructions using the RNeasy plus micro kit (Qiagen). RNA-Seq library preparation was performed using the Illumina TruSeq Stranded mRNA Kit, according to manufacturer's instructions, and sequenced with Illumina HiSeq 2000 Sequencer. Read quality was confirmed using FastQC v0.10.1 before alignment using TopHat v2.0.10 on the mouse GRCm38/mm10 genome.
SLAM receptors foster iNKT cell development by reducing TCR signal strength after positive selection.
Specimen part, Subject
View SamplesThe events regulating human preimplantation development are still largely unknown, due to scarcity of material, ethical and legal limitations, and lack of reliable techniques to faithfully amplify the transcriptome of a single cell. Nonetheless, knowledge in human embryology is gathering renewed interest due to its close relationship with both stem cell biology and epigenetic reprogramming to pluripotency, and their centrality to regenerative medicine. Using carefully timed genome-wide transcript analyses on single oocytes and embryos, the analysis of the data allowed us to uncover a series of successive waves of embryonic transcriptional initiation which start as early as the 2 cell stage. In addition, we identified hierarchical activation of genes involved in the regulation of pluripotency. Finally, we developed HumER, a free database of human preimplantation human development gene expression to serve the scientific community. Importantly, our work links early transcription in the human embryo with the correct execution of the pluripotency program later in development, and paves the way for the identification of factors to improve epigenetic reprogramming.
Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development.
Specimen part, Cell line
View SamplesParthenogenetic stem cells were derived from parthenotes, then differentiated to mesenchymal stem cells. These were further reprogrammed to induced pluripotent stem cells, which were finally differentiated to secondary mesenchymal stem cells.
Accumulation of instability in serial differentiation and reprogramming of parthenogenetic human cells.
Sex, Specimen part
View SamplesAcquired imatinib resistance in chronic myelogenous leukemia (CML) can be the consequence of mutations in the kinase domain of BCR-ABL or increased protein levels. However, as in other malignancies, acquired resistance to cytostatic drugs is a common reason for treatment failure or disease progression. As a model for drug resistance, we developed a CML cell line resistant to cyclophosphamide (CP). Using oligonucleotide arrays, we examined changes in global gene expression. Selected genes were also examined by real-time PCR and flow cytometry. Neither the parent nor the resistant lines had mutations in their ATP binding domain. Filtering genes with a low-base line expression, a total of 239 genes showed significant changes (162 up- and 77 down-regulated) in the resistant clone. Most of the up-regulated genes were associated with metabolism, signal transduction, or encoded enzymes. The gene for aldehyde dehydrogenase 1 was over-expressed more than 2000 fold in the resistant clone. BCR-ABL was expressed in both cell lines to a comparable extent. When exposed to the tyrosine kinase inhibitors imatinib and nilotinib, both lines were sensitive. In conclusion, we found multiple genetic changes in a CML cell line resistant to CP related to metabolism, signal transduction or apoptosis. Despite these changes, the resistant cells retained sensitivity to tyrosine kinase inhibitors.
Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors.
No sample metadata fields
View SamplesThe SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1.
SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.
Age, Specimen part
View SamplesInduced pluripotent stem (iPS) cells have generated interest for regenerative medicine as they allow for producing patient-specific progenitors in vitro with potential value for cell therapy. In many instances, however, an off-the-shelf approach would be desirable, such as for cell therapy of acute conditions or when the patient's somatic cells are altered as a consequence of chronic disease or aging. Cord blood (CB) stem cells appear ideally suited for this purpose as they are newborn, immunologically immature cells with minimal genetic and epigenetic alterations, and several hundred thousand immunotyped CB units are readily available through a worldwide network of CB banks. Here, we show that CB stem cells can be reprogrammed to pluripotency by retroviral transduction with OCT4, SOX2, KLF4, and c-MYC, in a process that is extremely efficient and fast. The resulting CB-derived iPS (CBiPS) cells are phenotypically and molecularly indistinguishable from human embryonic stem (hES) cells. Furthermore, we show that generation of CBiPS can be efficiently achieved without the use of the c-MYC and KLF4 oncogenes and just by overexpression of OCT4 and SOX2. Our studies set the basis for the creation of a comprehensive bank of HLA-matched CBiPS cells for off-the-shelf applications.
Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View SamplesTo unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sex, Specimen part
View Samples