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Updated: Sep 6, 2025
Isolation and Enrichment of Liver Progenitor Subsets Identified by a Novel Surface Marker Combination
Published on: February 18, 2017
Small-molecule inhibitor cocktail promotes the proliferation of pre-existing liver progenitor cells
Qingjie Fu1, Shunsuke Ohnishi2, Goki Suda1
1Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Abstract:
A recent study showed that a cocktail of three small molecules, Y-27632, A83-01, and CHIR99021 (YAC), converts mature hepatocytes (MHs) into proliferative bipotent cells that can be induced into MHs and cholangiocytes in rats. However, when we reproduced these experiments, it was found that bipotent cells may be derived from resident liver progenitor cells (LPCs), whose proliferative activity was promoted by YAC. A simple and efficient sorting scheme was also developed in this study to harvest high-purity and high-yield LPCs. The inducible bipotency of purified LPCs was verified; in addition, they were found to spontaneously differentiate into hepatocytes and cholangiocytes due to changes in proliferative status even without induction. Moreover, during the differentiation process, some hepatocytes spontaneously reconverted to LPCs under certain conditions, such as the release of contact inhibition. These findings may improve our understanding of LPCs and provide a cell source for regenerative medicine.
Insights
A small molecule cocktail (YAC) promotes liver progenitor cell (LPC) proliferation and bipotency in rats. Purified LPCs can differentiate into hepatocytes and cholangiocytes, offering potential for regenerative medicine.
Area of Science:
- Hepatology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Mature hepatocytes can be reprogrammed into bipotent progenitor cells using specific small molecules.
- Previous studies suggested direct conversion of hepatocytes, but the origin of bipotent cells remained unclear.
Purpose of the Study:
- To investigate the origin of bipotent cells generated by the YAC cocktail.
- To develop a method for isolating and characterizing liver progenitor cells (LPCs).
- To explore the differentiation potential and plasticity of LPCs.
Main Methods:
- Reproduction of experiments using a three-small-molecule cocktail (YAC: Y-27632, A83-01, CHIR99021).
- Development of a sorting scheme for high-purity and high-yield LPC isolation.
- Verification of inducible bipotency and spontaneous differentiation of purified LPCs.
- Observation of hepatocyte dedifferentiation into LPCs under specific conditions.
Main Results:
- Bipotent cells were found to originate from resident liver progenitor cells (LPCs), not directly from mature hepatocytes.
- YAC treatment significantly promoted the proliferation of LPCs.
- Purified LPCs demonstrated inducible bipotency and spontaneous differentiation into hepatocytes and cholangiocytes.
- Hepatocytes showed spontaneous reconversion to LPCs upon release from contact inhibition.
Conclusions:
- The YAC cocktail primarily expands resident liver progenitor cells (LPCs) rather than directly converting mature hepatocytes.
- Isolated LPCs possess inherent bipotency and plasticity, differentiating into hepatocytes and cholangiocytes.
- Understanding LPC behavior and plasticity offers insights into liver regeneration and potential cell sources for regenerative medicine.
