The generation of sufficient numbers of mature ventricular myocytes for effective cell-based therapy is a central barrier for cardiac regenerative medicine. Here we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes, and consistent with other reports of iPSCs derived from various somatic cell types, ventricular myocyte derived iPSCs (ViPSCs) exhibit a markedly higher propensity to differentiate into beating cardiomyocytes as compared to genetically-matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, ViPSC-derived cardiomyocytes form up to 99% ventricular myocytes suggesting that ventricular myocyte-derived iPSCs may be a viable strategy to generate specific cardiomyocyte subtypes for cell-based therapies. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the ventricular myocyte fate in pluripotent stem cells.
Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature.
Specimen part
View SamplesHuman survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global
A genomic storm in critically injured humans.
Sex, Age, Specimen part
View SamplesBlood was sampled from severe burns patients over time as well as healthy subjects. Genome-wide expression analyses were conducted using the Affymetrix U133 plus 2.0 GeneChip.
Genomic responses in mouse models poorly mimic human inflammatory diseases.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Specimen part, Cell line, Treatment, Subject
View SamplesPhysiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma.
A genomic score prognostic of outcome in trauma patients.
Sex, Age
View SamplesWe report here the genes that are sequentially expressed in white blood cells from blood and spleen at 2 hours, 2 day,3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Includes WBC treated with LPS for 2 hours and 1 day.
Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice.
Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Subject, Time
View SamplesOligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens. However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus (bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans.
A network-based analysis of systemic inflammation in humans.
No sample metadata fields
View Samplesgene expression profiles of leukocytes from blood (WBCs) and spleen harvested at an early (two hours) time point after injury or sham injury in mice subjected to trauma-hemorrhage, burn injury or lipopolysaccharide (LPS)-infusion at three experimental sites
Commonality and differences in leukocyte gene expression patterns among three models of inflammation and injury.
No sample metadata fields
View SamplesThe role of stem cells in solid tumors remains controversial. In colorectal cancers (CRC), this is complicated by the conflicting top-down or bottom-up hypothesis of cancer initiation. We profiled the expressions of genes from the top (T) and bottom (B) fractions of the crypt in morphologically normal-appearing colonic mucosa (M) and contrasted this to that of matched mucosa adjacent to tumors (MT) in twenty three sporadic CRC patients. In thirteen patients, the genetic distance (M-MT) between the B fractions is smaller than the distance between the T fractions indicating that the expressions of significant genes diverge further in the top fractions (B<T). In the remaining ten patients, the reverse is observed (B>T).
Human colorectal cancer initiation is bidirectional, and cell growth, metabolic genes and transporter genes are early drivers of tumorigenesis.
Specimen part
View Samples