Similar Datasets
Project description:Non-alcoholic steatohepatitis (NASH) is associated with hepatic steatosis, intralobular inflammation, and fibrosis. The degree of hepatic fibrosis, mainly caused by excessive production of extracellular matrix proteins, is the sole predictor of liver-related and overall mortality in NASH patients. The hepatic stellate cells (HSCs) are causally implicated in fibrogenesis during NASH development but as sinusoidal pericytes also vital for vascular homeostasis of the healthy liver. Using single-cell RNA-sequencing we have analyzed whole liver plasticity and interrogated the transition of HSCs from pericytes in the healthy liver to collagen-producing cells in a diet-induced murine model of advanced NASH. We show how postprandial cues are sensed and integrated by HSCs promoting their phenotypic stabilization and, through paracrine mediators, sinusoidal health. While dominant under healthy conditions the basis for this multimodal signaling through stellate cell-specific Gs protein-coupled receptors and the bile-acid receptor NR1H4/FXR deteriorates in activated HSCs of the NASH liver. Expression of key signaling components were validated in situ in human and murine liver tissue supporting the translatability of our findings and pharmacological relevance in treatment of chronic liver diseases as NASH.
2023-11-21 | GSE218298 | GEO
Project description:Non-alcoholic steatohepatitis (NASH) is associated with hepatic steatosis, intralobular inflammation, and fibrosis. The degree of hepatic fibrosis, mainly caused by excessive production of extracellular matrix proteins, is the sole predictor of liver-related and overall mortality in NASH patients. The hepatic stellate cells (HSCs) are causally implicated in fibrogenesis during NASH development but as sinusoidal pericytes also vital for vascular homeostasis of the healthy liver. Using single-cell RNA-sequencing we have analyzed whole liver plasticity and interrogated the transition of HSCs from pericytes in the healthy liver to collagen-producing cells in a diet-induced murine model of advanced NASH. We show how postprandial cues are sensed and integrated by HSCs promoting their phenotypic stabilization and, through paracrine mediators, sinusoidal health. While dominant under healthy conditions the basis for this multimodal signaling through stellate cell-specific Gs protein-coupled receptors and the bile-acid receptor NR1H4/FXR deteriorates in activated HSCs of the NASH liver. Expression of key signaling components were validated in situ in human and murine liver tissue supporting the translatability of our findings and pharmacological relevance in treatment of chronic liver diseases as NASH.
2023-11-21 | GSE218297 | GEO
Project description:Here we profile the transcripts of app. 32.000 single cells isolated from livers of healthy mice fed with a chow diet and diseased mice fed with a western diet for 52 weks. We analyzed the fibrogenic transition of HSCs from pericytes to collagen-producing cells, interrogated the NASH-associated rerouting of mononuclear phagocytes and uncovered novel aspects of cellular palsticity during more advanced stages of NASH. We reveal Stellate cell-specific Gs-protein-coupled receptors and the bile-acid receptor NR1H4/FXR seemingly dominated HSC biology in the healthy liver, forming the basis for multimodal diurnal signaling, but deteriorated in activated HSCs in advanced NASH. In addition to two emerging populations of Trem2-expressing monocyte-derived macrophages we found a population of CD207-positive macrophages significantly expanded in advanced NASH and likely derived from both incoming monocytes and Kupffer cells. Our work illustrates the emmense plasticity liver cells undergo upon induction of NASH, and potentially map novel treatment targets
2023-11-21 | GSE218296 | GEO
Project description:Non-alcoholic steatohepatitis (NASH) is associated with hepatic steatosis, intralobular inflammation, and fibrosis. The degree of hepatic fibrosis, mainly caused by excessive production of extracellular matrix proteins, is the sole predictor of liver-related and overall mortality in NASH patients. The hepatic stellate cells (HSCs) are causally implicated in fibrogenesis during NASH development but as sinusoidal pericytes also vital for vascular homeostasis of the healthy liver. Using single-cell RNA-sequencing we have analyzed whole liver plasticity and interrogated the transition of HSCs from pericytes in the healthy liver to collagen-producing cells in a diet-induced murine model of advanced NASH. We show how postprandial cues are sensed and integrated by HSCs promoting their phenotypic stabilization and, through paracrine mediators, sinusoidal health. While dominant under healthy conditions the basis for this multimodal signaling through stellate cell-specific Gs protein-coupled receptors and the bile-acid receptor NR1H4/FXR deteriorates in activated HSCs of the NASH liver. Expression of key signaling components were validated in situ in human and murine liver tissue supporting the translatability of our findings and pharmacological relevance in treatment of chronic liver diseases as NASH.
2023-11-21 | GSE218295 | GEO
Project description:Non-alcoholic steatohepatitis (NASH) is associated with hepatic steatosis, intralobular inflammation, and fibrosis. The degree of hepatic fibrosis, mainly caused by excessive production of extracellular matrix proteins, is the sole predictor of liver-related and overall mortality in NASH patients. The hepatic stellate cells (HSCs) are causally implicated in fibrogenesis during NASH development but as sinusoidal pericytes also vital for vascular homeostasis of the healthy liver. Using single-cell RNA-sequencing we have analyzed whole liver plasticity and interrogated the transition of HSCs from pericytes in the healthy liver to collagen-producing cells in a diet-induced murine model of advanced NASH. We show how postprandial cues are sensed and integrated by HSCs promoting their phenotypic stabilization and, through paracrine mediators, sinusoidal health. While dominant under healthy conditions the basis for this multimodal signaling through stellate cell-specific Gs protein-coupled receptors and the bile-acid receptor NR1H4/FXR deteriorates in activated HSCs of the NASH liver. Expression of key signaling components were validated in situ in human and murine liver tissue supporting the translatability of our findings and pharmacological relevance in treatment of chronic liver diseases as NASH.
2023-11-21 | GSE218299 | GEO
Project description:Non-alcoholic steatohepatitis (NASH) is associated with hepatic steatosis, intralobular inflammation, and fibrosis. The degree of hepatic fibrosis, mainly caused by excessive production of extracellular matrix proteins, is the sole predictor of liver-related and overall mortality in NASH patients. The hepatic stellate cells (HSCs) are causally implicated in fibrogenesis during NASH development but as sinusoidal pericytes also vital for vascular homeostasis of the healthy liver. Using single-cell RNA-sequencing we have analyzed whole liver plasticity and interrogated the transition of HSCs from pericytes in the healthy liver to collagen-producing cells in a diet-induced murine model of advanced NASH. We show how postprandial cues are sensed and integrated by HSCs promoting their phenotypic stabilization and, through paracrine mediators, sinusoidal health. While dominant under healthy conditions the basis for this multimodal signaling through stellate cell-specific Gs protein-coupled receptors and the bile-acid receptor NR1H4/FXR deteriorates in activated HSCs of the NASH liver. Expression of key signaling components were validated in situ in human and murine liver tissue supporting the translatability of our findings and pharmacological relevance in treatment of chronic liver diseases as NASH.
2023-02-01 | GSE207309 | GEO
Project description:Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module
| PRJNA854663 | ENA
Project description:Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module
| PRJNA903123 | ENA
Project description:Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module
| PRJNA903120 | ENA
Project description:Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module
| PRJNA903115 | ENA