Similar Datasets
Project description:Effects of exercise on gene expression level in human monocytes
2025-01-24 | E-GEOD-51835 | ExpressionAtlas
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:1. Evaluate the diagnostic value of long noncoding RNA (CCAT1) expression by RT-PCR in peripheral blood in colorectal cancer patients versus normal healthy control personal.
2. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in diagnosis of colorectal cancer patients & its relation to tumor staging.
3. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in precancerous colorectal diseases.
4. Compare long noncoding RNA (CCAT1) expression with traditional marker; carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) in diagnosis of colorectal cancer.
| 2330122 | ecrin-mdr-crc
Project description:Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of mRNAs, ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA-Seq and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro derived MK cells and these platelet-enriched transcripts are broadly occupied by ribosomes. We use RNA sequencing of synchronized populations of in vitro derived platelet-like particles (PLPs) to show that mRNA decay strongly shapes the nascent platelet transcriptome. Our data suggests that the decay of platelet mRNAs is slowed by the natural loss of the mRNA surveillance and ribosome rescue factor Pelota (PELO).
2017-02-02 | GSE94384 | GEO
Project description:Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. They have been identified historically by the cell surface expression of CD14 and CD16. However, recent single-cell studies have revealed that they are much more heterogeneous than previously realized. We utilized cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to describe the comprehensive transcriptional and phenotypic landscape of 437,126 monocytes. This high-dimensional multimodal approach identified vast phenotypic diversity and functionally distinct subsets, including IFN-responsive, MHCIIhi, monocyte-platelet aggregates, as well as non-classical, sand several subpopulations of classical monocytes. Using flow cytometry, we validated the existence of MHCII+CD275+ MHCIIhi, CD42b+ monocyte-platelet aggregates, CD16+CD99- non-classical monocytes, and CD99+ classical monocytes. Each subpopulation exhibited unique characteristics, developmental trajectories, transcriptional regulation, and tissue distribution. In addition, alterations associated with cardiovascular disease (CVD) risk factors, including race, smoking, and hyperlipidemia were identified. Moreover, the effect of hyperlipidemia was recapitulated in mouse models of elevated cholesterol. This integrative and cross-species comparative analysis provides a new perspective on comparison of alterations in monocytes in pathological conditions and offers insights into monocyte-driven mechanisms in CVD and the potential for monocyte subpopulation targeted therapies.
2025-05-08 | GSE296624 | GEO
Project description:Primary objectives: To evaluate the effect of iron therapy on platelet counts in patients with colorectal cancer and iron deficiency
Primary endpoints: drop in platelet counts>10%
| 2531118 | ecrin-mdr-crc
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:Platelets contain non-coding RNAs (ncRNAs), and their measurement may complement aggregometry. In the community-based Bruneck Study (N = 338), we conducted over 2,700 aggregometry measurements and over 65,000 RT-qPCR measurements in platelet releasates, platelet-poor plasma and isolated platelets. We show agonist-specific, dose-dependent platelet ncRNA release that is inhibited by aspirin. Collagen induces the strongest release for most ncRNAs, while miR-150 is hyperresponsive to ADP and miR-21 is hyperresponsive to arachidonic acid. Inflammation and high leukocyte-derived RNA content in platelets correlate inversely with platelet aggregation and platelet ncRNA release after stimulation. This inverse correlation is not observed in aspirin users. Finally, we reveal that platelet-derived microRNAs and YRNAs are carried by proteins and readily released, while circular RNAs, long non-coding RNAs and messenger RNAs are carried by vesicles and preferentially retained. Our findings provide evidence that inflammation leads to platelet pre-activation in vivo resulting in platelet exhaustion ex vivo.
2023-08-09 | GSE240195 | GEO
Project description:<p><strong>BACKGROUND:</strong> SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.</p><p><strong>METHODS:</strong> We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS and CD14 changes.</p><p><strong>RESULTS:</strong> Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.</p><p><strong>CONCLUSION:</strong> Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.</p>
1970-01-01 | MTBLS9136 | MetaboLights