Landscape of intercellular crosstalk in fatty liver disease revealed by single-cell secretome analysis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA531644 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8869110.fastq.gz | Fastqsanger.gz | |||
| SRR8869105.fastq.gz | Fastqsanger.gz | |||
| SRR8869107.fastq.gz | Fastqsanger.gz | |||
| SRR8869108.fastq.gz | Fastqsanger.gz | |||
| SRR8869109.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Cell-cell communications via ligand-receptor signaling are a fundamental feature of complex organs. In addition to hepatocytes, the mammalian liver harbors several distinct cell types, including endothelial cells, hepatic stellate cells (HSC), cholangiocytes, the resident macrophage Kupffer cells, and other immune cells, collectively known as non-parenchymal cells (NPC) 1-5. Paracrine signaling among NPC is important for tissue homeostasis and has been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), an emerging epidemic linked to metabolic syndrome 6-8. Despite this, the global landscape of intercellular signaling in the liver has not been comprehensively elucidated. Here we perform single-cell RNA sequencing and secretome analysis on liver NPC isolated from healthy and diet-induced NASH mice. Our analysis revealed highly specific patterns of the cellular sources of secreted ligands and membrane receptors and a network of paracrine and autocrine signaling at the single-cell level. Comparative analysis of secretome gene expression uncovered a global disruption of the liver endothelial signaling network during NASH pathogenesis. The HSC secretome encompasses extracellular matrix proteins, signaling ligands (stellakines) and three distinct functional classes of membrane receptors. Liver macrophage undergoes a marked expansion in NASH with the emergence of a new population marked by expression of Triggering receptor expressed on myeloid cells 2 (Trem2) and activation of a transcriptional program underlying phagocytosis, lysosomal degradation and antigen presentation. These results provide a high-resolution blueprint of intercellular crosstalk in mammalian liver and illustrate the complexity and richness of cell-cell signaling in liver physiology and disease.
2019-08-08 | GSE129516 | GEO
Project description:Intercellular crosstalk within human preimplantation lineages regulates Trophectoderm specification
| PRJNA1174731 | ENA
Project description:Cell-cell communication via ligand-receptor signaling is a fundamental feature of complex organs. Despite this, the global landscape of intercellular signaling in mammalian liver has not been elucidated. Here we perform single-cell RNA sequencing on non-parenchymal cells isolated from healthy and NASH mouse livers. Secretome gene analysis revealed a highly connected network of intrahepatic signaling and disruption of vascular signaling in NASH. We uncovered the emergence of NASH-associated macrophages (NAMs), which are marked by high expression of triggering receptors expressed on myeloid cells 2 (Trem2), as a feature of mouse and human NASH that is linked to disease severity and highly responsive to pharmacological and dietary interventions. Finally, hepatic stellate cells (HSCs) serve as a hub of intrahepatic signaling via HSC-derived stellakines and their responsiveness to vasoactive hormones. These results provide unprecedented insights into the landscape of intercellular crosstalk and reprogramming of liver cells in health and disease.
| S-EPMC7262680 | biostudies-literature
Project description:Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma
| PRJNA870065 | ENA
Project description:Physical activity is a powerful physiologic stimulus that provides benefits to multiple organ systems and confers protection against disease. These physiologic effects are in part mediated by blood-borne factors that mediate tissue crosstalk and function as molecular effectors of physical activity. To globally understand how physical activity reshapes cellular secretomes, here we applied a proximity biotinylation approach to profile cell type-specific secretomes from blood plasma following treadmill running in mice. This organism-wide, 21-cell type, 10-tissue in-vivo secretome atlas reveals complex cell type-specific and bidirectional modulation of secreted proteins across all cell types following exercise training. We identify a gradient of secretome responses across cell types, with secretomes from Pdgfra+ being one of the most exercise-responsive in the entire dataset. Peptide-level correlation analysis revealed widespread and cell type-specific exercise regulation of secreted proteoforms. Finally, we show that exercise-inducible secretion of soluble CES2 proteins from the liver suppresses obesity in high fat diet-fed mouse models. Together, these data identify specific exercise-regulated cell types and secreted proteins and illuminate the dynamic remodeling of cell and tissue crosstalk by physical activity.
2023-07-21 | PXD034535 | Pride
Project description:Endothelial-immune crosstalk contributes to vasculopathy in nonalcoholic fatty liver disease
| PRJNA745465 | ENA
Project description:Cardiovascular complications are major causes of death in non-alcoholic fatty liver disease (NAFLD) but the underlying endothelial pathophysiology remains understudied. Here, we cultivated blood outgrowth endothelial cells (BOECs) from NAFLD patients and healthy controls. Our transcriptomic analysis revealed that NAFLD BOECs were activated with chemokine hallmarks, in particular, enhanced CXCL12 was confirmed in arterial tissues of mouse NAFLD models. Immunoprofiling by single-cell analysis further uncovered T cell intensification and potentially T-helper type 1 inflammatory reactions in NAFLD. In evaluating CXCL12-CXCR4 axis in chemotaxis, CXCR4 antagonist (AMD3100) substantially modulated the migration of CD4+ Tcells, natural killer cells and monocytes towards NAFLD BOECs, which was not observed in healthy control coculture. We found that NAFLD and healthy BOECs might preferentially recruit distinct subsets of immune cells, as a result of unique chemokine ligand-receptor interactions. Finally, we enumerated two folds more circulating endothelial cells, a biomarker of vascular injury, in NAFLD patients than healthy subjects. Our work provides insights for modulation of endothelial-immune crosstalk as an avenue for mitigating endothelial dysfunction in NAFLD.
2022-04-11 | GSE179886 | GEO
Project description:Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post59 translational cancer hallmark and the consequences thereof remain elusive. Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In both cancer cell cultures and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycomes revealed that fucosylation of the antioxidant PON1 is a critical component of the therapy66 induced secretome. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Non-specific and PON1-specific secretome deglycosylation both limited the expansion of resistant clones in a tumor regression model. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance.
2023-04-05 | GSE160205 | GEO
Project description:Endothelial-immune crosstalk contributes to vascular injury in non-alcoholic fatty liver disease
| PRJNA747248 | ENA
Project description:Cardiovascular complications are major causes of death in non-alcoholic fatty liver disease (NAFLD) but the underlying endothelial pathophysiology remains understudied. Here, we cultivated blood outgrowth endothelial cells (BOECs) from NAFLD patients and healthy controls. Our transcriptomic analysis revealed that NAFLD BOECs were activated with chemokine hallmarks, in particular, enhanced CXCL12 was confirmed in arterial tissues of mouse NAFLD models. Immunoprofiling by single-cell analysis further uncovered T cell intensification and potentially T-helper type 1 inflammatory reactions in NAFLD. In evaluating CXCL12-CXCR4 axis in chemotaxis, CXCR4 antagonist (AMD3100) substantially modulated the migration of CD4+ T cells, natural killer cells and monocytes towards NAFLD BOECs, which was not observed in healthy control coculture. We found that NAFLD and healthy BOECs might preferentially recruit distinct subsets of immune cells, as a result of unique chemokine ligand-receptor interactions. Finally, we enumerated two folds more circulating endothelial cells, a biomarker of vascular injury, in NAFLD patients than healthy subjects. Our work provides insights for modulation of endothelial-immune crosstalk as an avenue for mitigating endothelial dysfunction in NAFLD.
2022-04-12 | GSE180241 | GEO