Platelets facilitate primary progressive tuberculosis by restricting the oxidative burst in phagocytes
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ABSTRACT:
PROVIDER: PRJNA565413 | ENA |
REPOSITORIES: ENA
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Project description:Tuberculosis (TB) remains the leading cause of death by a single infectious agent worldwide. Despite decades of active research, host factors which underly susceptibility to Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, are still ill defined. We investigated the role of platelets (PLTs) during primary TB in mice as these cells were recently assigned multiple immunological functions. PLTs were present at the site of infection, formed aggregates with different myeloid subsets during experimental TB and such aggregates were detected also in TB patients. PLTs were detrimental during the early phase of infection and this effect was uncoupled from their canonical activation. PLTs left lung cell dynamics and patterns of anti-mycobacterial T-cell responses unchanged. PLTs hampered cell autonomous defense by restricting production of reactive oxygen species (ROS) in lung residing myeloid cells. Thus, PLTs orchestrate immunity in TB by modulating innate immune responsiveness during primary lung infection and may be amenable to new interventions for this deadly disease.
2020-12-22 | GSE137421 | GEO
Project description:We sequenced allele-resolution single-cell transcriptomes from mouse primary fibroblasts and embryonic stem cells with the overall aim to infer transcriptional kinetics for each gene and allele. Inferred transcriptional burst kinetics revealed the genomic encoding of transcriptional burst frequencies and sizes within the genome. Core promoter elements were found to specify burst sizes, whereas burst frequencies were regulated by enhancers. In particular burst frequencies were found to account for cell-type differences in gene expression levels and were also mostly correlating with absolute expression levels in cells. Importantly, the patterns identified were not detectable at the level of mean expression demonstrating the need to investigate transcriptional dynamics at the level of burst kinetics.
2018-11-30 | E-MTAB-7098 | biostudies-arrayexpress
Project description:Sorted Mouse Phagocytes RNAseq
| PRJNA417315 | ENA
Project description:Despite abundant evidence demonstrating that platelets foster metastasis, anti- platelet agents have low therapeutic potential due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subjected syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases via immune suppression. Genetic depletion and pharmacological targeting of the platelet-specific receptor GPVI in humanized mouse models efficiently reduced the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study is the first to demonstrate therapeutic efficacy when targeting animals bearing growing metastases. It further identifies GPVI as the first molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.
2024-03-10 | E-MTAB-13864 | biostudies-arrayexpress
Project description:Platelets are blood cells who play critical roles in numerous biological and disease processes. This study was designed to identify lncRNAs that may play a role in platelet reactivity. In this study, by using large-scale deep sequencing, we determined the expression profiles of lncRNAs in both hyperreactive and hyporeactive human platelets. To determine the potential link between the expression of lncRNAs and the function of platelets, the expression profiles of hyperreactive and hyporeactive platelets were compared. Compared with hyperreactive platelets, deep sequencing analysis demonstrated that differential lncRNA expression was a remarkable characteristic in hyporeactive platelets.
2020-04-02 | GSE97348 | GEO
Project description:Thrombopoietin (TPO) acting via its receptor Mpl is the major cytokine regulator of platelet number. To precisely define the role of specific hematopoietic cells in TPO dependent hematopoiesis, we generated mice that express the Mpl receptor normally on stem/progenitor cells but lack expression on megakaryocytes and platelets (MplPF4cre/PF4cre). MplPF4cre/PF4cre mice displayed profound megakaryocytosis and thrombocytosis with a remarkable expansion of megakaryocyte-committed and multipotential progenitor cells, the latter displaying biological responses and a gene expression signature indicative of chronic TPO over-stimulation as the underlying causative mechanism, despite a normal circulating TPO level. Thus, TPO signaling in megakaryocytes is dispensable for platelet production; its key role in control of platelet number is via generation and stimulation of the bipotential megakaryocyte precursors. Nevertheless, Mpl expression on megakaryocytes and platelets is essential to prevent megakaryocytosis and myeloproliferation by restricting the amount of TPO available to stimulate the production of megakaryocytes from the progenitor cell pool.
2014-06-10 | E-MTAB-2389 | biostudies-arrayexpress
Project description:Early diagnosis of acute myeloid leukemia (AML) in the pre-leukemic stage remains a clinical challenge, as pre-leukemic patients show no symptoms, lacking any known morphological or numerical abnormalities in blood cells. Here, we demonstrate that platelets with structurally abnormal mitochondria emerge at the pre-leukemic phase of AML, preceding detectable changes in blood cell counts or detection of leukemic blasts in blood. We visualized frozen-hydrated platelets from mice at different time points during AML development in situ using electron cryo-tomography (cryo-ET) and identified intracellular organelles through an unbiased semi-automatic process followed by quantitative measurement. A large proportion of platelets exhibited changes in the overall shape and depletion of organelles in AML. Notably, 23% of platelets in pre-leukemic cells exhibit abnormal, round mitochondria with unfolded cristae, accompanied by a significant drop in ATP levels and altered expression of metabolism-related gene signatures. Our study demonstrates that detectable structural changes in pre-leukemic platelets may serve as a biomarker for the early diagnosis of AML.
2022-02-08 | GSE189844 | GEO
Project description:Identification of differentially expressed genes in intestinal phagocytes, compared to non-intestinal cells in Schmidtea mediterranea. Total RNA was isolated from either intestinal phagocytes or non-intestinal cells (control). Four independent biological replicates were conducted with two dye swaps. Labeled targets were hybridized to two oligonucleotide arrays on which 11,521 planarian transcripts were represented.
2012-10-01 | E-GEOD-35565 | biostudies-arrayexpress
Project description:We used single-cell RNA-sequencing to generate allele-resolution expression levels in individual cells that we used for inference of transcriptional burst kinetics.
2018-09-30 | E-MTAB-6362 | biostudies-arrayexpress
Project description:Platelets are small anucleate cells derived from the fragmentation of megakaryocytes and are involved in different biological processes especially hemostasis, thrombosis and immune response. Platelet purification is a crucial step in transcriptomic analysis, and researchers usually encounter the problem of platelet contamination by leukocytes and erythrocytes. Leukocytes contain much more RNA than platelets, thus the presence of few contaminants in platelet preparation can strongly alter transcriptome results. Using microarray technique, we compared transcriptome of platelets from the same donor, purified by common centrifugation method or using magnetic microbeads to eliminate contaminating cells.
2022-03-31 | GSE193664 | GEO