Single-cell profiles of peripheral blood mononuclear cell (PBMC) and bone marrow mononuclear cell (BMMC) from pneumosepsis mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE262512 | GEO | 2024/05/20
REPOSITORIES: GEO
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Project description:Systemic immune cells dysregulation, especially the inflammatory factors over-production plays the pivotal role in sepsis induced abnormalities. We further analyzed how HDCA affects the systemic immune cells during sepsis by employing scRNA-seq for PBMCs.
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Project description:Single-cell profiles of peripheral blood mononuclear cell (PBMC) and bone marrow mononuclear cell (BMMC) from pneumosepsis mice
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Project description:The wide array of molecules carried by plasma regulates critical immune functions and constitutes valuable biomarkers and therapeutic targets. In recent years the introduction of “systems approaches” has provided investigators with powerful means for assessing immune responses in patient samples on a global scale. However, while the use of genome-wide profiling technologies has become widespread, measuring the plasma proteome still presents considerable challenges. An alternative approach that consists in measuring transcriptome responses in reporter cells exposed in vitro to patient plasma has been successfully employed in a limited number of studies. Here we devised such a “Transcriptomic Reporter Assay” system to assess the immunogenicity of plasma from septic patients and evaluate its potential for biomarker discovery. Sepsis is a common, severe systemic infectious process for which physicians still lack efficient diagnostic or prognostic tools. Of the three different cell reporter systems tested, neutrophils were identified as the most capable “plasma sensor”. Compared to peripheral blood mononuclear cells and dendritic cell preparations neutrophils were best able to discriminate between plasma from septic and control subjects and responded by upregulating a robust immune transcriptional program. Additionally, the amplitude of the neutrophil transcriptomic response was shown to be associated with disease severity in two additional sets of patients. Overall, our results demonstrate both the suitability and potential clinical relevance of a neutrophil reporter assay for assessing immunopathogenic processes in a complex and severe condition such as sepsis. Peripheral blood mononuclear cells (PBMCs) were isolated from two healthy donors. Plasma samples were obtained from patients with culture-confirmed sepsis (n=12) and from uninfected controls (n=12). PBMCs were cultured for 6 h in medium alone, plasma from patients with sepsis, plasma from uninfected controls, and LPS using a final concentration of 20%. Transcriptional profiles were acquired using Illumina HumanHT12 V4 BeadChips.
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Project description:Pregnancy is an immune paradox: where the mother accepts a semi-allograft/allograft (donor embryo), while avoiding maternal immune suppression. Indeed, impaired development of maternal immune tolerance towards the conceptus may be an important cause of implantation failure and pregnancy loss. Successful implantation rates for allogenic donor embryos are unexpectedly high, while abnormal embryos may be unable to initiate maternal tolerance, suggesting that embryo-specific compounds can play a vital role in this process. Both a tolerant T-suppressor (TH2), and inflammatory, T-helper 1 (TH1) cytokine profiles are an integral part of pregnancy and the viable embryo/fetus plays a critical role in creating this delicate balance. Maternal recognition of pregnancy occurs prior to implantation. There were several embryo derived factors reported. However, we previously found that preimplantation factor (PIF) is distinct from the other non-pregnancy-specific embryo-derived factors. Herein we aimed to characterize PIF and examine its role in early pregnancy events by observing the isolated novel peptide's effect on human Peripheral Blood Mononuclear Cell (PBMC). We did affymetrix, GeneChip Human Genome U133 plus 2.0 array on RNA isolated from normal human PBMC cultured for 24hrs in the presence or absence of PIF to study the genes modulated by PIF.
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Project description:BACKGROUND Many patients are not responsive or tolerant to medical therapies for carotid atherosclerosis. Thus, elucidating the molecular mechanism for the pathogenesis and progression of carotid atherosclerosis and identifying new potential molecular targets for medical therapies that can slow progression of carotid atherosclerosis and prevent ischemic events are quite important. MATERIAL AND METHODS We downloaded the expression profiling data of PBMC in Biobank of Karolinska Endarterectomy (BiKE, GSE21545) for GEO. The WGCNA and DEG screening were conducted. The co-expression pattern between patients with ischemic events (the events group) and patients without ischemic events (the no-events group) were compared. Then, we identified hub genes of each module. Finally, the DEG co-expression network was constructed and MCODE was used to identify crucial genes based on this co-expression network. RESULTS In the study, 183 DEGs were screened and 8 and 6 modules were assessed in the events group and no-events group, respectively. Compared to the no-events group, genes associated with inflammation and immune response were clustered in the green-yellow module of the events group. The hub gene of the green-yellow module of the events group was KIR2DL5A. We obtained 1 DEG co-expression network, which has 16 nodes and 24 edges, and we detected 5 crucial genes: SIRT1, THRAP3, RBM43, PEX1, and KLHDC2. The upregulated genes (THRAP3 and RBM43) showed potential diagnostic and prognostic value for the occurrence of ischemic events. CONCLUSIONS We detected 8 modules for the events group and 6 modules for the no-events group. The hub genes for modules and crucial genes of the DEG co-expression network were also identified. These genes might serve as potential targets for medical therapies and biomarkers for diagnosis and prognosis. Further experimental and biological studies are needed to elucidate the role of these crucial genes in the progression of carotid atherosclerosis.
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Project description:Although an increase in studies has revealed the potential mechanisms underlying immune dysfunction during CKD progression, there are still many significant components that need to be clarified, such as the machinery of T-cell phenotype switching and the plasticity levels of different subsets. Fortunately, in the last decade, novel technologies such as single-cell RNA sequencing have enabled us to investigate transcriptomic profiles at the single-cell level and have enabled us to unravel the potential mechanisms of the heterogeneity of the cell phenotype underlying different diseases. In this study, we investigated the immune cell composition, function, and interaction with other cells in PBMCs (peripheral blood mononuclear cells) during the ESRD period, especially CD4+ T-cell plasticity and the involved signaling pathways and mediators, which could be potential therapeutic targets for preventing CKD progression and complications.
2023-10-31 | GSE233315 | GEO
Project description:Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multi-organ failure. Therapeutic options to prevent sepsis-associated immunopathology remain scarce. Here, we established a mouse model of long-lasting disease tolerance during severe sepsis, manifested by diminished immunothrombosis and organ damage in spite of a high pathogen burden. We found that, both neutrophils and B cells emerged as key regulators of tissue integrity. Enduring changes in the transcriptional profile of neutrophils, included upregulated Cxcr4 expression in protected, tolerant hosts. Neutrophil Cxcr4 upregulation required the presence of B cells, suggesting that B cells promoted disease tolerance by improving tissue damage control via the suppression of neutrophils’ tissue damaging properties. Finally, therapeutic administration of a Cxcr4 agonist successfully promoted tissue damage control and prevented liver damage during sepsis. Our findings highlight the importance of a critical B-cell/neutrophil interaction during sepsis and establish neutrophil Cxcr4 activation as a potential means to promote disease tolerance during sepsis.
2022-08-04 | GSE210207 | GEO
Project description:BackgroundThe knowledge about blood circulating microbiome and its functional relevance in healthy individuals remains limited. An assessment of changes in the circulating microbiome was performed by sequencing peripheral blood mononuclear cells (PBMC) bacterial DNA from goats supplemented or not in early life with rumen liquid transplantation.ResultsMost of the bacterial DNA associated to PBMC was identified predominantly as Proteobacteria (55%) followed by Firmicutes (24%), Bacteroidetes (11%) and Actinobacteria (8%). The predominant genera found in PBMC samples were Pseudomonas, Prevotella, Sphingomonas, Acinetobacter, Corynebacterium and Ruminococcus. Other genera such as Butyrivibrivio, Bifidobacterium, Dorea and Coprococcus were also present in lower proportions. Several species known as blood pathogens or others involved in gut homeostasis such as Faecalibacterium prausnitzii were also identified. However, the PBMC microbiome phylum composition differed from that in the colon of goats (P ≤ 0.001), where Firmicutes was the predominant phylum (83%). Although, rumen liquid administration in early-life altered bacterial community structure and increased Tlr5 expression (P = 0.020) in colon pointing to higher bacterial translocation, less than 8% of OTUs in colon were also observed in PBMCs.ConclusionsData suggest that in physiological conditions, PBMC microbiome differs from and is not affected by colon gut microbiota in small ruminants. Although, further studies with larger number of animals and covering other animal tissues are required, results point to a common circulating bacterial profile on mammals being phylum Proteobacteria, and genera Pseudomonas and Prevotella the most abundants. All suggest that PBMC microbiome in healthy ruminants could be implicated in homeostatic condition. This study expands our knowledge about PBMC microbiome contribution to health in farm animals.
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