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Related Experiment Video

Updated: Feb 26, 2026

Cell Type-specific Gene Expression Profiling in the Mouse Liver

Cell Type-specific Gene Expression Profiling in the Mouse Liver

Published on: September 17, 2019

Single-cell Spatial Transcriptomics Reveals Hepatocyte Reprogramming in Fontan Associated Liver Disease.

Brandon M Lehrich¹, Jordann N Lewis², Vik Meadows¹

¹Organ Pathobiology and Therapeutics Institute, University of Pittsburgh School of Medicine, Pittsburgh, United States of America.

|February 24, 2026

Summary

This summary is machine-generated.

This study reveals a new type of stressed hepatocyte in Fontan-associated liver disease (FALD). These cells show disrupted liver zonation and increased heat shock protein 70, correlating with fibrosis severity.

Keywords:

Cardiology Cardiovascular disease Cell stress Cellular senescence Hepatology Metabolism

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Area of Science:

Cardiovascular Research
Hepatology
Single-cell Biology

Background:

Fontan-associated liver disease (FALD) is a common complication in patients with single ventricle physiology after the Fontan operation.
The progression and underlying mechanisms of FALD remain poorly understood, impacting clinical management.

Purpose of the Study:

To investigate the cellular and molecular pathophysiology of Fontan-associated liver disease (FALD) progression.
To identify novel cell populations and signaling pathways involved in FALD development using advanced spatial transcriptomics.

Main Methods:

Single-cell spatial transcriptomics (CosMx™) was applied to liver explant tissues from FALD patients.
Immunofluorescence staining was used to validate protein expression and assess liver zonation and cellular stress markers.
Bioinformatic analyses including cell clustering and pathway analysis (CellChat) were performed.

Main Results:

Twelve distinct liver cell types were identified, including six hepatocyte subtypes.
Advanced FALD showed an expansion of mid-zonal hepatocytes and a loss of canonical zonal markers.
A novel 'zonally ambiguous and stressed hepatocyte' population was identified, exhibiting increased cellular stress and heat shock protein 70 (HSP70) expression.
Ectopic WNT2 signaling was implicated in disrupting hepatocyte zonation.
HSP70 expression strongly correlated with the Congestive Hepatic Fibrosis (CHF) score.

Conclusions:

Single-cell spatial transcriptomics identified a unique stressed hepatocyte population in advanced FALD.
Disrupted liver zonation and increased cellular stress, marked by HSP70, are key features of FALD progression.
Further research into hepatocyte metabolic function is crucial for understanding FALD in Fontan patients.