Identification of a Rare Gli1 Progenitor Cell Population Contributing to Liver Regeneration During Chronic Injury

Overview

Journal Cell Discov

Date 2022 Nov 1

PMID 36316325

Authors

Jiayin Peng

Fei Li

Jia Wang

Chaoxiong Wang

Yiao Jiang

Biao Liu

Juan He

Kai Yuan

Chenyu Pan

Moubin Lin

Bin Zhou

Luonan Chen

Dong Gao

Yun Zhao

Affiliations

Soon will be listed here.

Abstract

In adults, hepatocytes are mainly replenished from the existing progenitor pools of hepatocytes and cholangiocytes during chronic liver injury. However, it is unclear whether other cell types in addition to classical hepatocytes and cholangiocytes contribute to hepatocyte regeneration after chronic liver injuries. Here, we identified a new biphenotypic cell population that contributes to hepatocyte regeneration during chronic liver injuries. We found that a cell population expressed Gli1 and EpCAM (EpCAMGli1), which was further characterized with both epithelial and mesenchymal identities by single-cell RNA sequencing. Genetic lineage tracing using dual recombinases revealed that Gli1 nonhepatocyte cell population could generate hepatocytes after chronic liver injury. EpCAMGli1 cells exhibited a greater capacity for organoid formation with functional hepatocytes in vitro and liver regeneration upon transplantation in vivo. Collectively, these findings demonstrate that EpCAMGli1 cells can serve as a new source of liver progenitor cells and contribute to liver repair and regeneration.

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