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Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into Hepatocytes.

Abstract：

:Chronic liver injury can cause cirrhosis and impaired liver regeneration, impairing organ function. Adult livers can regenerate in response to parenchymal insults, and multiple cellular sources have been reported to contribute to this response. In this study, we modeled human chronic liver injuries, in which such responses are blunted, without genetic manipulations, and assessed potential contributions of non-parenchymal cells (NPCs) to hepatocyte regeneration. We show that NPC-derived hepatocytes replenish a large fraction of the liver parenchyma following severe injuries induced by long-term thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment. Through lineage tracing of biliary epithelial cells (BECs), we show that BECs are a source of new hepatocytes and gain an Hnf4α+CK19+ bi-phenotypic state in periportal regions and fibrotic septa. Bi-phenotypic cells were also detected in cirrhotic human livers. Together, these data provide further support for hepatocyte regeneration from BECs without genetic interventions and show their cellular plasticity during severe liver injury.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Deng X,Zhang X,Li W,Feng RX,Li L,Yi GR,Zhang XN,Yin C,Yu HY,Zhang JP,Lu B,Hui L,Xie WF

doi

10.1016/j.stem.2018.05.022

subject

Has Abstract

pub_date

2018-07-05 00:00:00

pages

114-122.e3

issue

1

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(18)30240-6

journal_volume

23

pub_type

杂志文章

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