Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205320 | GEO | 2022/08/02
REPOSITORIES: GEO
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Project description:We utilized CITESeq to investigate changes in immune cell frequencies and their transcriptomic signatures in PBMCs obtained from subjects with low and high coronary artery disease (CAD) severity quantified using gensini scoring system as well as subjects with and without IgE to alpha-gal sensitization
2022-02-02 | GSE190570 | GEO
Project description:Background: Atherosclerosis (AS)-associated cardiovascular disease is an important cause of mortality in an aging population of people living with HIV (PLWH). This elevated risk of atherosclerosis has been attributed to viral infection, prolonged usage of anti-retroviral therapy, and subsequent chronic inflammation. Methods: To investigate dysregulated immune signaling in PLWH with and without AS, we sequenced 9368 peripheral blood mononuclear cells (PBMCs) from 8 PLWH, 4 of whom also had atherosclerosis (AS+). To develop executable models of signaling pathways that drive cellular states in HIV-associated atherosclerosis, we developed the single-cell Boolean Omics Network Invariant Time Analysis (scBONITA) algorithm. ScBONITA (a) uses single-cell RNA sequencing data to infer Boolean rules for topologically characterized networks, (b) prioritizes genes based on their impact on signaling, (c) performs pathway analysis, and (d) maps sequenced cells to characteristic signaling states. We used scBONITA to identify dysregulated pathways in different cell-types from AS+ PLWH and AS- PLWH. To compare our findings with pathways associated with HIV infection, we used scBONITA to analyze a publicly available dataset of PBMCs from subjects before and after HIV infection. Additionally, the executable Boolean models characterized by scBONITA were used to analyze observed cellular states corresponding to the steady states of signaling pathways Results: We identified an increased subpopulation of CD8+ T cells and a decreased subpopulation of monocytes in AS+ PLWH. Dynamic modeling of signaling pathways and pathway analysis with scBONITA provided a new perspective on the mechanisms of HIV-associated atherosclerosis. Lipid metabolism and cell migration pathways are induced by AS rather than by HIV infection. These pathways included AGE-RAGE and PI3K-AKT signaling in CD8+ T cells, and glucagon and cAMP signaling pathways in monocytes. Further analysis of other cell subpopulations suggests that the highly interconnected PI3K-AKT signaling pathway drives cell migratory state in response to dyslipidemia. scBONITA attractor analysis mapped cells to pathway-specific signaling states that correspond to distinct cellular states. Conclusions: Dynamic network modeling and pathway analysis with scBONITA indicates that dysregulated lipid signaling regulates cell migration into the vascular endothelium in AS+ PLWH. Attractor analysis with scBONITA facilitated pathway-based characterization of cellular states that are not apparent in gene expression analyses.
2022-09-06 | GSE198339 | GEO
Project description:We used Affymetix HG Focus GeneChip to measure the expression levels of HIV seronegative and seropositive individuals in human PBMCs in vivo. GSM39104 -GSM39115 are HIV seronegative samples; GSM39116-GSM39137 are HIV seropositive but drug naive samples; GSM39138-GSM39147 are HIV seropositive samples used to test serostatus biomarker; GSM39148-GSM39170 are HIV seropositive individuals whose CD4 cells decrease over time; GSM39171-GSM39187 are HIV seropositive individuals whose CD4 cells increase over time; GSM39188-GSM39190 are HIV seropositive samples used to test CD4 cell increase/decrease over time.
2007-08-25 | E-GEOD-2171 | biostudies-arrayexpress
Project description:Cellular composition and responsiveness of immune system evolve upon ageing and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit decreased viral replication ex vivo compared to men. We thus hypothesized that these findings could be recapitulated in vitro, and infected primary CD4+ T cells with HIV-based vectors pseudotyped with VSV-G or HIV envelopes. We used cells isolated from twenty donors to interrogate the effect of sex and age on permissiveness over a six-day activation kinetics. Our data identified an increased permissiveness to HIV between 24 and 72h post-stimulation. Sex- and age-based analysis at these time points showed increased susceptibility to HIV of cells isolated from males and from donors over 50 years old, respectively. Parallel assessment of surface marker expression revealed higher frequencies of activation markers (CD69, CD25, HLA-DR) and immune check point inhibitors (PD-1 and CTLA-4 in cells from highly permissive donors. Furthermore, positive correlations were identified between CD69, PD-1 and CTLA-4 expression kinetics and HIV expression kinetics. Cell population heterogeneity was assessed by single-cell RNA-Seq analysis and no cell subtype enrichment was identified according to sex. Finally, transcriptomic analyses further highlighted the role of activation in those differences with enriched activation and cell cycle gene sets in men and in older women cells. Altogether, this study brought further evidence about individual features affecting HIV replication at the cellular level and should be considered in latency reactivation studies for HIV cure.
2023-12-13 | GSE247485 | GEO
Project description:Cellular composition and responsiveness of immune system evolve upon ageing and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit decreased viral replication ex vivo compared to men. We thus hypothesized that these findings could be recapitulated in vitro, and infected primary CD4+ T cells with HIV-based vectors pseudotyped with VSV-G or HIV envelopes. We used cells isolated from twenty donors to interrogate the effect of sex and age on permissiveness over a six-day activation kinetics. Our data identified an increased permissiveness to HIV between 24 and 72h post-stimulation. Sex- and age-based analysis at these time points showed increased susceptibility to HIV of cells isolated from males and from donors over 50 years old, respectively. Parallel assessment of surface marker expression revealed higher frequencies of activation markers (CD69, CD25, HLA-DR) and immune check point inhibitors (PD-1 and CTLA-4 in cells from highly permissive donors. Furthermore, positive correlations were identified between CD69, PD-1 and CTLA-4 expression kinetics and HIV expression kinetics. Cell population heterogeneity was assessed by single-cell RNA-Seq analysis and no cell subtype enrichment was identified according to sex. Finally, transcriptomic analyses further highlighted the role of activation in those differences with enriched activation and cell cycle gene sets in men and in older women cells. Altogether, this study brought further evidence about individual features affecting HIV replication at the cellular level and should be considered in latency reactivation studies for HIV cure.
2023-12-13 | GSE247484 | GEO
Project description:Single cell multi-omic sequencing (CITEseq) of human peripheral blood mononuclear cells (PBMCs)
| PRJNA787578 | ENA
Project description:People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.
2024-03-21 | PXD046510 | Pride
Project description:HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning this effect are not well investigated. Our main objective is to detect gene expression alterations in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least one month of CBD treatment. We collected PBMCs from three HIV-positive subjects at baseline and after CBD treatment (at least 27 days) via single-cell RNA sequencing. We obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells. Our study shows how CBD is associated with alterations of gene expression in myeloid cells after CBD treatment.
2023-03-31 | GSE228652 | GEO
Project description:We investigated if differences in host gene expression modulate the size of the total HIV-1 PBMC reservoir during suppressive ART. Individuals treated with ART during acute infection who demonstrated effective viral suppression but varying frequencies of HIV-1 DNA+ cells were characterized by single-cell RNA sequencing (scRNA-seq). Differentially expressed genes and enriched pathways demonstrated increased monocyte activity in participants with undetectable HIV-1 reservoirs. This was validated in an independent study cohort comprised of 38 participants with different genetic backgrounds and HIV-1 subtype infections.
2025-01-29 | GSE256089 | GEO
Project description:It is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used cryopreserved peripheral blood mononuclear cells (PBMC) from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were unpaired, with one sample per person, after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC. Treatment adherence was based on plasma TDF concentrations. Covariates included Nugent scores (for bacterial vaginosis), HSV-2 serology, age, and birth control method. Levels of natural and synthetic hormones (medroxyprogesterone acetate [MPA], estradiol [E2], ethinyl estradiol [EE2], levonorgestrel [LNG], etonogestrel [ENG], progesterone [P4], and norethisterone enanthate [NET-EN]) were measured in the serum. 1. Lund, J. M. et al. HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. J. Virol. 90, 9855–9861 (2016). 2. Baeten, J. M. et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367, 399–410 (2012).
2020-07-07 | GSE139411 | GEO