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| Status |
Public on Nov 21, 2023 |
| Title |
Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
10x Genomics single-cell transcriptomic data of isolated liver cells from healthy (52w chow diet) and diseased (52w Western Diet) mice.
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| Contributor(s) |
Bendixen SM, Sørensen PR, Terkelsen MK, Hansen D, Hejn KH, Bjerre FA, Thulesen AP, Eriksen NG, Hailenberg P, Dam TV, Larsen FT, Wernberg CW, Vijayathurai J, Scott EA, Marcher A, Detlefsen S, Grøntved L, Dimke H, lauridsen MM, Krag AA, Blagoev B, Ravnskjaer K |
| Citation(s) |
37972658 |
| Submission date |
Nov 18, 2022 |
| Last update date |
Nov 22, 2023 |
| Contact name |
Kim Ravnskjaer |
| E-mail(s) |
ravnskjaer@bmb.sdu.dk
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| Organization name |
University of Southern Denmark
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| Department |
Biochemistry and Molecular Biology
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| Lab |
Ravnskjaer lab
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| Street address |
Campusvej 55
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| City |
Odense M |
| ZIP/Postal code |
5230 |
| Country |
Denmark |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| GSM6738781 |
NASH Liver cells, Western Diet 52w, rep A |
| GSM6738782 |
NASH Liver cells, Western Diet 52w, rep B |
| GSM6738783 |
NASH Liver cells, Western Diet 52w, rep C |
| GSM6738784 |
NASH Liver cells, Western Diet 52w, rep D |
| GSM6738785 |
NASH Liver cells, Western Diet 52w, rep E |
| GSM6738786 |
NASH Liver cells, Western Diet 52w, rep F |
| GSM6738787 |
Control Liver cells, Chow Diet 52w, rep A |
| GSM6738788 |
Control Liver cells, Chow Diet 52w, rep B |
| GSM6738789 |
Control Liver cells, Chow Diet 52w, rep C |
| GSM6738790 |
Control Liver cells, Chow Diet 52w, rep D |
| GSM6738791 |
Control Liver cells, Chow Diet 52w, rep E |
| GSM6738792 |
Control Liver cells, Chow Diet 52w, rep F |
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| This SubSeries is part of SuperSeries: |
| GSE218300 |
Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module |
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| Relations |
| BioProject |
PRJNA903120 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE218299_RAW.tar |
204.0 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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