Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish.
Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish.
复制标题
DOI：
10.1172/jci.insight.163929
复制
发表时间：
2023-01-10
期刊：
影响因子：
8
通讯作者：
Goessling, Wolfram
中科院分区：
文献类型：
--
作者：
Oderberg, Isaac M.;Goessling, Wolfram
The liver is a highly regenerative organ, yet the presence of a dedicated stem cell population remains controversial. Here, we interrogate a severe hepatocyte injury model in adult zebrafish to define that regeneration involves a stem cell population. After near-total hepatocyte ablation, single-cell transcriptomic and high-resolution imaging analyses throughout the entire regenerative timeline reveal that biliary epithelial cells undergo transcriptional and morphological changes to become hepatocytes. As a population, biliary epithelial cells give rise to both hepatocytes and biliary epithelial cells. Biliary epithelial cells proliferate and dedifferentiate to express hepatoblast transcription factors prior to hepatocyte differentiation. This process is characterized by increased MAPK, PI3K, and mTOR signaling, and chemical inhibition of these pathways impairs biliary epithelial cell proliferation and fate conversion. We conclude that, upon severe hepatocyte ablation in the adult liver, biliary epithelial cells act as facultative liver stem cells in an EGFR-PI3K-mTOR–dependent manner.
登录
查看更多内容
影响因子：
64.8
作者：
Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
通讯作者：
Itzkovitz S
影响因子：
21.3
作者：
D'Uva, Gabriele;Aharonov, Alla;Tzahor, Eldad
通讯作者：
Tzahor, Eldad
影响因子：
11
作者：
Amali, AA;Rekha, RD;Wu, JL
通讯作者：
Wu, JL
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
9.3
作者：
Adler, Miri;Kohanim, Yael Korem;Alon, Uri
通讯作者：
Alon, Uri