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| Status |
Public on Jul 19, 2021 |
| Title |
A human liver cell-based system modeling a clinical prognostic liver signature combined with single-cell RNA-Seq for discovery of liver disease therapeutics |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Abstract: Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. We developed a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in NASH-HCC animal models and patient-derived tumorspheroids, we identified nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Perturbation studies combined with scRNA-Seq analyses of patient liver tissues uncovered HRH2+, CLEC5Ahigh, MARCOlow liver macrophages and hepatocytes as nizatidine targets. The PLS model combined with scRNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention.
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| Overall design |
We performed bulk RNA sequencing of DMSO differentiated Huh751 at different time points
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| Contributor(s) |
Crouchet E, Zhu S, Hoshida Y, Baumert TF |
| Citation(s) |
34535664 |
| Submission date |
Mar 17, 2021 |
| Last update date |
Jun 29, 2022 |
| Contact name |
Shijia Zhu |
| E-mail(s) |
shijia.zhu@utsouthwestern.edu
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| Organization name |
University of Texas Southwestern Medical Center
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| Street address |
5323 Harry Hines Blvd
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| City |
DALLAS |
| State/province |
Texas |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE66843 |
A cell-based model unravels drivers for hepatocarcinogenesis and targets for clinical chemoprevention |
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| Relations |
| BioProject |
PRJNA715183 |
| SRA |
SRP311067 |
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