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Updated: Jun 14, 2026

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
Published on: April 18, 2025
β-catenin regulates mesenchymal progenitor cell differentiation during hepatogenesis
Tove Berg1, Stijn DeLanghe, Denise Al Alam
1Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA.
Background:
Understanding the pathways regulating mesenchymal progenitor cell fate during hepatogenesis may provide insight into postnatal liver injury or liver bioengineering. While β-Catenin has been implicated in the proliferation of fetal hepatic epithelial progenitor cells, its role in mesenchymal precursors during hepatogenesis has not been established.
Materials And Methods:
We used a murine model of conditional deletion of β-Catenin in mesenchyme using the Dermo1 locus (β-Catenin(Dermo1)) to characterize the role of β-Catenin in liver mesenchyme during hepatogenesis.
Results:
Lineage tracing using a LacZ reporter indicates that both hepatic stellate cells and pericytes derive from mesenchymal Dermo1 expressing precursor cells. Compared to control littermate livers, β-Catenin(Dermo1) embryonic livers are smaller and filled with dilated sinusoids. While the fraction of mesenchymally-derived cells in β-Catenin(Dermo1) embryos is unchanged compared to littermate controls, there is an increase in the expression of the mesenchymal markers, DESMIN, α-SMA, and extracellular deposition of COLLAGEN type I, particularly concentrated around dilated sinusoids. Analysis of the endothelial cell compartment in β-Catenin(Dermo1)/Flk1(lacZ) embryos revealed a marked reorganization of the intrahepatic vasculature. Analysis of various markers for the endodermally-derived hepatoblast population revealed marked alterations in the spatial expression pattern of pan-cytokeratin but not E-cadherin, or albumin. β-Catenin(Dermo1) phenocopies mesenchymal deletion of Pitx2, a known regulator of hepatic mesenchymal differentiation both during both organogenesis and postnatal injury.
Conclusions:
Our data implicate mesenchymal β-Catenin signaling pathway in the differentiation of liver mesenchymal progenitor cells during organogenesis, possibly via Pitx2. Hepatic mesenchymal β-Catenin signaling, in turn, modulates the development of both endothelium and endodermally-derived hepatoblasts, presumably via other downstream paracrine pathways.
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