KRAS mutations are the ost abundand driver mutations found in lung adenocarcinoma patients. Unfortunately, there are no clinical approved inhibitors available, to directly target mutant forms of KRAS. The aim of the study was to unravel the impact of upstream Egfr activation in signaling of mutated K-ras. We found that upregulation of G12D mutant Kras induced genes was significantly impaired when Egfr was knocked out. Our data suggests that signaling of mutant Kras depends on upstream activation. This finding may be exploited therapeutically by targeting EGFR in KRAS mutant patients. Overall design: We isolated mouse alveolar type II cells and induced the Kras G12D mutation, with and without concomitant Egfr knockout, in vitro. Cells lysates were analyzed 5 days following transgene induction.
JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression.
Specimen part, Cell line, Subject
View SamplesIn the hematopoietic microenvironment, endothelial cells (ECs) play an important role in the regulation of hematopoietic cell proliferation and trafficking. We previously demonstrated that EC stimulated with tumor necrosis factor alpha (TNF-) induce the generation of dendritic cells from CD34(+) stem cells, whereas in contrast, interleukins were capable of inducing the proliferation of hematopoietic and myeloid progenitors.
Transcriptional profiling of the hematopoietic support of interleukin-stimulated human umbilical vein endothelial cells (HUVECs).
Specimen part, Treatment
View SamplesComplete identification of the bone marrow niche remains one of the most progressing fields. Attempts to identify soluble factors involved in stem cell renewal have been less successful. We have previously shown that endothelial cells (EC) can induce the long-term proliferation of hematopoietic progenitor cells (HPC), especially when they had been subjected to an inflammatory stimulus like interleukins (IL) 1.
Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity.
Specimen part, Treatment, Time
View SamplesIn response to elevated glucocorticoid levels, erythroid progenitors rapidly expand to produce large numbers of young erythrocytes. Previous work demonstrates hematopoietic changes in rodents exposed to various physical and psychological stressors, however, the effects of chronic psychological stress on erythropoiesis has not be delineated. We employed laboratory, clinical and genomic analyses of a murine model of chronic restraint stress (RST) to examine the influence of psychological stress on erythropoiesis. Mice exposed to RST demonstrated markers of early erythroid expansion involving the glucocorticoid receptor. In addition, these RST-exposed mice had increased numbers of circulating reticulocytes and increased erythropoiesis in primary and secondary erythroid tissues. Mice also showed increases in erythroid progenitor populations and elevated expression of the erythroid transcription factor KLF1 in these cells. Together this work describes some of the first evidence of psychological stress affecting erythroid homeostasis through glucocorticoid stimulation and begins to define the transcription factor pathway involved.
Chronic restraint stress upregulates erythropoiesis through glucocorticoid stimulation.
Sex
View SamplesLymph node vs. tonsil
Differential expression of a gene signature for scavenger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis.
No sample metadata fields
View SamplesVaccinia virus infection of mouse lungs produces a focal infection within the lung remaining at the large bronchi throughout the course of infection. Animals die of respiratory failure with little edema and few infiltrating immune cells. It is well established that poxviruses control the host immune system by encoding multiple host defense pathway antagonists.
Roles of vaccinia virus genes E3L and K3L and host genes PKR and RNase L during intratracheal infection of C57BL/6 mice.
Specimen part
View SamplesLow-oxygen stress associated with natural phenomena such as waterlogging, results in widespread transcriptome changes and a metabolic switch from aerobic respiration to anaerobic fermentation. High-throughput sequencing of small RNA libraries obtained from low-oxygen stressed and control root tissue identified a total of 65 unique microRNA (miRNA) sequences from 46 families, and 14 trans-acting small interfering RNA (tasiRNA) from 3 families. Low-oxygen stress resulted in changes to the abundance of 46 miRNAs from 19 families, and all 3 tasiRNA families. Chemical inhibition of mitochondrial respiration caused similar changes in expression in a majority of the low-oxygen responsive small RNAs analysed. Our data indicate that miRNAs and tasiRNAs play a role in gene regulation and possibly developmental responses to low oxygen, and that a major signal for these responses is likely to be dependent on mitochondrial function. Keywords: Small RNA transcriptome analysis Overall design: Examination of root tissue under 2 different environments, control and low oxygen
Hypoxia-responsive microRNAs and trans-acting small interfering RNAs in Arabidopsis.
Age, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
Specimen part
View SamplesWe compared differences in fetal and adult T cells by performing whole genome profiling on sort-purified T cells (nave CD4+ and Treg cells) from human fetal specimens (18-22 gestational weeks) and adult specimens (age 25-40 years old). Fetal and Adult Nave CD4+ T cells phenotype: CD3+CD4+CD45RA+CCR7+CD27+, Fetal and Adult CD4+CD25+ Treg phenotype: CD3+CD4+CD25bright
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
Specimen part
View SamplesHuman fetal and adult hematopoietic stem cells (HSC) were obtained from fetal liver, fetal bone marrow (BM), and adult BM. These were injected into human fetal thymic implants in SCID-hu Thy/Liv mice (4-6 separate mice per HSC donor) and allowed to mature into single positive CD4+ (SP4) thymocytes over the course of 7-8 weeks. SP4 thymocytes from injected stem cells were subsequently sort-purified from thymic implants and gene expression was performed.
Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
Specimen part
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