In 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 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 SamplesRetinopathy of prematurity (ROP) is a disorder of the developing retina of preterm infants. ROP can lead to blindness due to abnormal angiogenesis that is the result of suspended vascular development and vaso-obliteration leading to severe retinal stress and hypoxia. We tested the hypothesis that a combined treatment with two human progenitor populations, the CD34+ cells, bone marrow-derived, and the endothelial colony-forming cells (ECFCs) synergistically protected the developing retinal vasculature in a murine model of ROP, the oxygen-induced retinopathy (OIR)., CD34+ cells alone, ECFCs alone, or a combination thereof were injected intravitreally at either P5 or P12 and pups were euthanized at P17. Retinas from OIR mice injected with ECFCs or the combined treatment revealed formation of the deep vascular plexus (DVP) while still in hyperoxia, with normal appearing connections between the superficial vascular plexus (SVP) and the DVP. The combination therapy prevented aberrant retinal neovascularization and was more effective anatomically and functionally at rescuing the ischemia phenotype than either cell type alone. The beneficial effect of the cell combination was the result of their ability to orchestrate an acceleration of vascular development and more rapid ensheathment of pericytes on the developing vessels.
Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model.
Specimen part, Disease, Disease stage, Treatment
View SamplesMicrovesicles (MV) are small membrane-bound particles comprised of exosomes and various sized extracellular vesicles. These are released by a number of cell types. Microvesicles have a variety of cellular functions from communication to mediating growth and differentiation. Microvesicles contain proteins and nucleic acids. Previously, we showed that plasma microvesicles contain microRNAs (miRNAs). Based on our previous report, the majority of peripheral blood microvesicles are derived from platelets while mononuclear phagocytes, including macrophages, are the second most abundant population. Here, we characterized macrophage-derived microvesicles and whether they influenced the differentiation of nave monocytes. We also identified the miRNA content of the macrophage-derived microvesicles. We found that RNA molecules contained in the macrophage-derived microvesicles were transported to target cells, including monocytes, endothelial cells, epithelial cells and fibroblasts. Furthermore, we found that miR-223 was transported to target cells and was functionally active. Based on our observations, we hypothesize that microvesicles bind to and activate target cells. Furthermore, we find that microvesicles induce the differentiation of macrophages. Thus, defining key components of this response may identify novel targets to regulate host defense and inflammation.
Macrophage microvesicles induce macrophage differentiation and miR-223 transfer.
Specimen part, Treatment
View SamplesSequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10 and C18) and parental PEO1 (P1 and P2) cells was performed in order to determine mechanisms of acquired resistance in the resistant cell lines. PEO1 parental cell lines were authenticated prior to sequencing. PEO1 parental were confirmed to be BRCA2-mutated (5139C>G). Olaparib PEO1 resistant cells were generated through a step-wise escalation of olaparib (10nM to 8uM olaparib). In olaparib resistant lines an increase canonical Wnt signaling and loss of of non-canonical Wnt signaling was observed. Overall design: Sequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10, and C18) and parental PEO1 cells was performed in order to determine mecahnisms of acquired resistance.
Activation of Wnt signaling promotes olaparib resistant ovarian cancer.
Cell line, Subject
View SamplesLNCaP cells were maintained in charcoal-stripped serum containing medium for 48 hours and treated with vehicle or 10 uM of UT-69, UT-155, R-UT-155, or enzalutamide. Twenty four hours after treatment, the cells were harvested, RNA was isolated and expression of genes was measured using microarray (Affymetrix Clarion S)
Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer.
Cell line
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 SamplesElectroacupuncture is the combination of traditional acupuncture and modern electrotherapy. Here we provide a mechanism for the beneficial effects of electroacupuncture and show that stimulation of the equine acupoints LI-4, LI-11 and GV-14 and Bai-hui results in mobilization of mesenchymal stem cells (MSCs) into the systemic circulation, which was accompanied by a time-dependent increase in plasma levels of norepinephrine (p=0.02). MSC differentiation was preferentially directed towards osteogenic rather than adipogenic lineages. Additionally, MSCs enhanced arterialization of blood vessels in vivo when implanted with human endothelial colony forming cells in oligomeric collagen matrices in NOD/SCID mice. When compared to equine bone marrow-derived MSCs or to equine adipose-tissue-derived MSCs, through the use of a microarray, these cells clustered separately. The electroacupuncture -mobilized cells showed increased expression of genes involved in cell growth and proliferation, compared to the bone marrow cells. These findings provide a new insight into the mechanism of the beneficial effects of acupuncture. Our findings suggest the involvement of neuronal regulation in the mobilization of reparative MSCs, and use of electroacupuncture at these designated points may be considered to treat acute and chronic inflammation following injury for which MSCs have been deemed beneficial.
Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells.
Specimen part, Treatment
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.
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