Single-cell RNA sequencing reveals a novel inhibitory effect of ApoA4 on NAFL mediated by liver-specific subsets of myeloid cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA875932 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21390326_1.fastq.gz | Fastqsanger.gz | |||
| SRR21390326_2.fastq.gz | Fastqsanger.gz | |||
| SRR21390327_1.fastq.gz | Fastqsanger.gz | |||
| SRR21390327_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:The liver immune microenvironment is a key element in the development of hepatic inflammation in NAFLD. However, the precise immune cell subsets that exacerbate fatty liver remain elusive. ApoA4 deficiency increases the hepatic lipid burden, insulin resistance, and metabolic inflammation. The aim of this study was to profile the hepatic immune cells affected by ApoA4 in NAFL. We performed scRNA-seq on liver immune cells from WT and ApoA4-deficient mice administered a high-fat diet.
2022-10-25 | GSE212546 | GEO
Project description:The liver immune microenvironment is a key element in the development of hepatic inflammation in NAFLD. ApoA4 deficiency increases the hepatic lipid burden, insulin resistance, and metabolic inflammation. However, the effect of ApoA4 on liver immune cells and the precise immune cell subsets that exacerbate fatty liver remain elusive. The aim of this study was to profile the hepatic immune cells affected by ApoA4 in NAFL. We performed scRNA-seq on liver immune cells from WT and ApoA4-deficient mice administered a high-fat diet. Immunostaining and qRT-PCR analysis were used to validate the results of scRNA-seq. We identified 10 discrete immune cell populations comprising macrophages, DCs, granulocytes, B, T and NK&NKT cells and characterized their subsets, gene expression profiles, and functional modules. ApoA4 deficiency led to significant increases in the abundance of specific subsets, including inflammatory macrophages (2-Mφ-Cxcl9 and 4-Mφ-Cxcl2) and activated granulocytes (0-Gran-Wfdc17). Moreover, ApoA4 deficiency resulted in higher Lgals3, Ctss, Fcgr2b, Spp1, Cxcl2, and Elane levels and lower Nr4a1 levels in hepatic immune cells. These genes were consistent with human NAFLD-associated marker genes linked to disease severity. The expression of NE and IL-1β in granulocytes and macrophages as key ApoA4 targets were validate in the presence or absence of ApoA4 by immunostaining. The scRNA-seq data analyses revealed reprogramming of liver immune cells resulted from ApoA4 deficiency. We uncovered that the emergence of ApoA4-associated immune subsets (namely Cxcl9+ macrophage, Cxcl2+ macrophage and Wfdc17+ granulocyte), pathways, and NAFLD-related marker genes may promote the development of NAFL. These findings may provide novel therapeutic targets for NAFL and the foundations for further studying the effects of ApoA4 on immune cells in various diseases.
| S-EPMC9678944 | biostudies-literature
Project description:We exploited label-free quantitative mass spectrometry to compare primary human blood Dendritic cells (DCs) subsets protein expression to identify new markers. Subsets distinguished are: Plasmacytoid DCs (pDC) and BDCA3+ and CD1c+ myeloid DCs and CD16+ monocytes. The dendritic cells were analyzed by LC-MS/MS and processed by MaxQuant for identification and LFQ quantification.
2016-09-27 | PXD004678 | Pride
Project description:Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype. In summary, regulatory myeloid DC and macrophages may play a dual role during life-threatening granulomatous infections, such as tuberculosis: on one hand, regulatory myeloid cells promote pathogen containment by efficiently killing intracellular bacteria, on the other hand these cells inhibit granuloma-associated T cells and thereby might be involved in the retention of TNF-controlled granuloma integrity protecting the host from granuloma break-down and pathogen dissemination. Experiment Overall Design: Transcriptional profiles of immature mo-DC (immDC, n=3), mature stimulatory mo-DC (matDC, n=3) and mature inhibitory mo-DC either stimulated with prostaglandin E2 (PGE2-DC, n=3) or infected with L.monocytogenes (infDC, n=3) were compared on Affymetrix HG-U133A platform. All samples represent biological replicates and were processed separately throughout the experiment.
2008-11-07 | E-GEOD-9946 | biostudies-arrayexpress
Project description:The subsets of immune cells within the human placenta are incompletely described. We used microarray to determine the transcriptional differences between two myeloid subsets in the term human placenta.
2017-09-26 | GSE104224 | GEO
Project description:Balb/c donor hearts were transplanted into C57/BL6 recipients as previously described (Corry et al, 1973). Recipient mice were treated with 250μg anti-CD40L mAb for tolerance induction on days 0, 2, and 4 as previously described (Jiang et al., 2011) or left untreated. On day 5 after transplantation graft infiltrating myeloid subsets were isolated using fluorescence activated cell sorting (FACS). Affymetrix Mouse Gene arrays were run in triplicate with the samples of interest. Raw CEL file data from Affymetrix Expression Console were background corrected, normalized, and summarized using RMA. 18 Samples, 9 treated and 9 untreated, 3 replicates each
2015-09-01 | E-GEOD-68648 | biostudies-arrayexpress
Project description:Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. Inflammatory injury and aberrant repair processes contribute to the development of kidney fibrosis. Myeloid cells, particularly monocytes/macrophages, play a crucial role in kidney fibrosis by releasing their proinflammatory cytokines and extracellular matrix components such as collagen and fibronectin into the microenvironment of the injured kidney. Numerous signaling pathways have been identified in relation to these activities. However, the involvement of metabolic pathways in myeloid cell functions during the development of renal fibrosis remains understudied. In our study, we initially reanalyzed single-cell RNA sequencing data of renal myeloid cells from Dr. Denby’s group and observed an increased glycolytic pathway in myeloid cells that are critical for renal inflammation and fibrosis. To investigate the role of myeloid glycolysis in renal fibrosis, we utilized a model of unilateral ureteral obstruction in mice deficient of Pfkfb3, an activator of glycolysis, in myeloid cells (Pfkfb3ΔMϕ) and their wild type littermates (Pfkfb3WT). We observed a significant reduction in fibrosis in the obstructive kidneys of Pfkfb3ΔMϕ mice compared to Pfkfb3WT mice. This was accompanied by a substantial decrease in myeloid cell infiltration, as well as a decrease in the numbers of M1 and M2 macrophages and suppression of macrophage to obtain myofibroblast phenotype in the obstructive kidneys of Pfkfb3ΔMϕ mice. Mechanistic studies indicate that glycolytic metabolites stabilize HIF1α, leading to alterations in macrophage phenotypes that contribute to renal fibrosis. In conclusion, our study implicates that targeting myeloid glycolysis represents a novel approach to inhibit renal fibrosis.
2024-03-12 | MTBLS8278 | MetaboLights
Project description:The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS) including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. By combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifted towards clonal expansion. Finally, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain’s innate immune system.
2019-01-25 | GSE118948 | GEO
Project description:Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype. In summary, regulatory myeloid DC and macrophages may play a dual role during life-threatening granulomatous infections, such as tuberculosis: on one hand, regulatory myeloid cells promote pathogen containment by efficiently killing intracellular bacteria, on the other hand these cells inhibit granuloma-associated T cells and thereby might be involved in the retention of TNF-controlled granuloma integrity protecting the host from granuloma break-down and pathogen dissemination. Keywords: Cell type comparison, response to infection
2008-10-21 | GSE9946 | GEO
Project description:Balb/c donor hearts were transplanted into C57/BL6 recipients as previously described (Corry et al, 1973). Recipient mice were treated with 250μg anti-CD40L mAb for tolerance induction on days 0, 2, and 4 as previously described (Jiang et al., 2011) or left untreated. On day 5 after transplantation graft infiltrating myeloid subsets were isolated using fluorescence activated cell sorting (FACS). Affymetrix Mouse Gene arrays were run in triplicate with the samples of interest. Raw CEL file data from Affymetrix Expression Console were background corrected, normalized, and summarized using RMA.
2015-09-01 | GSE68648 | GEO