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Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System

Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System

Published on: May 10, 2020

Hepatic progenitor cells express SerpinB3.

Gianmarco Villano, Cristian Turato, Santina Quarta

¹Department of Medicine-DIMED, University of Padua, Via Giustiniani 2, Padua 35128, Italy. patrizia@unipd.it.

BMC Cell Biology

|February 13, 2014

Summary

SerpinB3 is highly expressed in hepatic stem/progenitor cells in both fetal and adult human livers. This finding is significant for understanding liver injury and cancer development.

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Isolation and Enrichment of Liver Progenitor Subsets Identified by a Novel Surface Marker Combination

Isolation and Enrichment of Liver Progenitor Subsets Identified by a Novel Surface Marker Combination

Published on: February 18, 2017

Area of Science:

Hepatology and stem cell biology
Molecular mechanisms of liver disease
Cancer research

Background:

Hepatic progenitor cells activate during liver injury, potentially leading to poor-prognosis tumors.
SerpinB3 (serine protease inhibitor B3) is overexpressed in injured liver and liver cancer.
SerpinB3 promotes apoptosis resistance, epithelial-mesenchymal transition, and influences TGF-beta and Myc signaling.

Purpose of the Study:

To investigate the presence and role of SerpinB3 in hepatic stem/progenitor cells.
To analyze SerpinB3 expression in human fetal and adult livers.
To examine SerpinB3 in a mouse model of liver stem/progenitor cell activation.

Main Methods:

Analysis of hepatic progenitor cells (EpCAM-positive) in human fetal and adult livers.
Immunohistochemistry on human cirrhotic livers.
Induction of liver stem/progenitor cell activation in C57BL/6J mice using lipopolysaccharide and D-galactosamine.
Time-course analysis of SerpinB3 expression and caspase 3 activity in mouse liver.
Transcriptional analysis and sequencing of mouse SerpinB3 isoforms.

Main Results:

SerpinB3 was detected in sorted EpCAM-positive progenitor cells from human fetal and adult livers.
Immunohistochemistry confirmed SerpinB3 in progenitor cells (CK-7, CK-19, EpCAM, CD-90 positive) in human cirrhotic livers.
In mice, SerpinB3 expression increased with liver injury, paralleled by a decrease in activated caspase 3.
Sequence analysis identified the mouse homolog as Serpinb3b.

Conclusions:

SerpinB3 is significantly expressed within the hepatic stem/progenitor cell compartment.
This expression is present in both fetal and adult liver progenitor cells.
The findings suggest a role for SerpinB3 in liver progenitor cell biology and potentially in liver disease pathogenesis.