Similar Datasets
Project description:Monocyte mRNA following incubation for 4 hrs with adult or P7 platelets
| PRJNA935400 | ENA
Project description:We seek to compare the mRNA profile of neonatal and adult platelets in mice
2024-02-15 | GSE225401 | GEO
Project description:Monocyte RNA after exposure to platelets
| PRJNA1078061 | ENA
Project description:CD14+ monocytes, the predominant population in human blood, are primarily engaged in host defense and pro-inflammatory cytokine responses. Aberrant monocyte activity causes life-threatening cytokine storms, while dysfunctional monocytes lead to 'immunoparalysis.' Understanding the mechanisms controlling monocyte functions is therefore paramount. Here, we reveal platelets' vital role in human monocytes' pro-inflammatory responses. Natural low platelet counts in patients with immune thrombocytopenia (ITP) , platelet depletion in healthy human monocytes, or in vivo platelet depletion in mice, result in monocyte immunoparalysis, characterized by reduced pro-inflammatory gene expression and weakened cytokine responses to immune challenge. Remarkably, supplementation with fresh platelets reverses monocyte immunoparalysis. In mice, thrombocytopenia results in down-regulation of myeloid innate immune genes, and compromised host defense transcriptional programs in monocytes despite normal responses to LPS. Platelets control monocyte cytokines independently of traditional cross-talk pathways, acting as reservoirs of transcription factors like NF?B and MAPK p38. We pinpointed a vesicle-derived NF?B2 transfer to human monocytes by mass spectrometry-based proteomics. Functionally, platelets proportionally restored impaired cytokine secretion in human monocytes lacking MAPK p38a and NF?B p65 and NF?B2. We unveil the intercellular transfer of inflammatory regulators, positioning platelets as central checkpoints in monocyte-mediated inflammation.
2024-08-14 | PXD052113 | Pride
Project description:It has been proposed that developmental differences exist between neonatal and adult platelets. Detailed insight therein is, however, still lacking. We have now compared the platelet protein expression profile of neonates and adults employing a label-free quantitative mass spectrometry approach. In addition, platelet aggregation mediated by thromboxane A2 analog, collagen, and peptide agonists of the protease-activated-receptors 1 and 4 was assessed. Results showed that neonatal platelets effectively aggregate in the presence the employed platelet agonists. In agreement with previous studies, higher concentrations of the agonists were required to initiate aggregation in the neonatal platelets. Mass spectrometry analysis revealed no significant difference in the expression level of critical adhesive platelet proteins like glycoprotein (GP)Ib, integrin αIIbβ3, GPV and GPIX. Neonatal platelets did show reduced expression levels of proteins involved in intracellular signaling, i.e. LYN, MAP3k5 and FAM129A. Several proteins that are known to be related to mitochondrial energy metabolism processes such as oxidative phosphorylation, i.e. NDUFS3, NDUFS8 and NDUFA1 were upregulated in neonates. In conclusion, this study reveals that the platelets derived from neonates and adults are distinct. In particular, developmental changes were observed for proteins that belong to metabolic and energy generation processes.
2021-02-05 | PXD004578 | Pride
Project description:Understanding the underlying mechanisms of the well-established platelet hyporeactivity in neonates, would be of great relevance for both improving the clinical management of neonates, a population with a higher bleeding risk than adults (especially among sick and preterm infants), and getting new insights onto the regulatory mechanisms of platelet biology. Transcriptome analysis is a useful tool to identify mRNA signature affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never been reported. Here, we used, for the first time, mRNA expression array to compare the platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories. A high correlation was obtained between arrays results for both adult and neonate platelet samples. There was also a good agreement between our adult results and those previously reported in three different studies. Gene enrichment analysis demonstrated that immunity- and platelet function-related genes are highly expressed in either developmental stage. Remarkably, 201 genes were found to be differentially expressed along development. In particular, neonatal platelets contain higher levels of mRNA that are associated with protein synthesis and processing, while they carry significantly lower levels of genes related with calcium transport/metabolism and cell signaling (including GNAZ). Overall, our results highlight that variations in platelet transcriptome may underline the hypo-functional phenotype of neonatal platelets, and further support the role of platelets in cellular immune response. A better characterization of the platelet transcriptome across development may help to elucidate the implications of transcriptome changes in different pathological conditions.
2017-02-03 | GSE94292 | GEO
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:Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) was then performed to establish the H3K4me3 landscape in neonatal and adult CD14+ monocytes. As development progressed from neonate to adult, monocytes gained the activating mark H3K4me3. The decreased H3K4me3 abundance at immunologically important neonatal monocyte gene promoters correlated with reduced gene expression, providing evidence that neonatal immune cells exist in an epigenetic state that is distinctly different from adults, and that this state contributes to neonatal specific immune responses.
2016-05-27 | GSE81957 | GEO
Project description:Extracellular vesicles (EV) convey biological messages through their cargoes. Herein we focus on monocyte/platelet aggregates characteristic of several cardiovascular diseases with an analysis of monocyte-derived EV (mEVs) effects on the atherosclerotic plaque. Monocyte preparations were stimulated with TNF-α in presence or absence of prostacyclin and EVs isolated via centrifugation. EV physical characteristics were determined by Nanoparticle Tracking analysis while surface profile was analysed using imaging flow cytometry. Atherosclerotic plaques from 5 patients undergoing endarterectomy were cultured with or without mEVs. Cytokines and proteins released in the culture media were measured by multiplex ELISA and mass spectrometry. Proteomic of mEVs prepared in different incubation settings was also conducted. Monocyte isolation yielded ~80% platelet-monocyte aggregates. TNF-α stimulation produced CD14+ EVs as well as a subset bearing the CD41 marker for platelets (CD14+/CD41+). Prostacyclin addition did not modulate monocyte/platelet aggregates, but impacted on mEV numbers. Addition of TNF-α mEVs on atherosclerotic plaque fragments impacted on general protein release (19 upregulated and 7 downregulated) and elevated cytokine release. mEVs generated by TNF-α and prostacyclin produced minimal changes on plaque reactivity. Proteomic analysis of mEVs revealed a distinctive composition when the cell preparation was activated with TNF-α alone or with prostacyclin. In conclusion, mEVs activate the atherosclerotic plaque. Attenuating platelet activation has an effect on EV composition with downstream modulation of their pro-inflammatory actions. EV heterogeneity reflects the mode of activation of the cell of origin and may differently contribute to the development and progression of atherosclerosis.
2021-09-08 | PXD014325 | Pride