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Evidence for in vitro extensive proliferation of adult hepatocytes and biliary epithelial cells.


ABSTRACT: Over the last several years, a method has emerged which endows adult hepatocytes with in vitro proliferative capacity, producing chemically-induced liver progenitors (CLiPs). However, a recent study questioned the origin of these cells, suggesting that resident liver progenitor cells, but not hepatocytes, proliferate. Here, we provide lineage tracing-based evidence that adult hepatocytes acquire proliferative capacity in vitro . Unexpectedly, we also found that the CLiP method allows biliary epithelial cells to acquire extensive proliferative capacity. Interestingly, after long-term culture, hepatocyte-derived cells (hepCLiPs) and biliary-derived cells (bilCLiPs) become similar in their gene expression patterns, and they both exhibit differentiation capacity to form hepatocyte-like cells. Finally, we provide evidence that hepCLiPs can repopulate chronically injured mouse livers, reinforcing our earlier argument that CLiPs can be a cell source for liver regenerative medicine. Moreover, this study offers bilCLiPs as a potential cell source for liver regenerative medicine.

SUBMITTER: Katsuda T 

PROVIDER: S-EPMC9881927 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Evidence for <i>in vitro</i> extensive proliferation of adult hepatocytes and biliary epithelial cells.

Katsuda Takeshi T   Li Jinyang J   Merrell Allyson J AJ   Sussman Jonathan J   Matsuzaki Juntaro J   Ochiya Takahiro T   Stanger Ben Z BZ  

bioRxiv : the preprint server for biology 20230103


Over the last several years, a method has emerged which endows adult hepatocytes with <i>in vitro</i> proliferative capacity, producing chemically-induced liver progenitors (CLiPs). However, a recent study questioned the origin of these cells, suggesting that resident liver progenitor cells, but not hepatocytes, proliferate. Here, we provide lineage tracing-based evidence that adult hepatocytes acquire proliferative capacity <i>in vitro</i> . Unexpectedly, we also found that the CLiP method allo  ...[more]

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