Wnt antagonist SFRP3 inhibits the differentiation of mouse hepatic progenitor cells.
Wnt/beta-catenin pathway plays an important role in regulating embryonic development. Hepatocytes differentiate from endoderm during development. Hepatic progenitor cells (HPCs) have been isolated from fetal liver and extrahepatic tissues. Most current studies in liver development and hepatic differentiation have been focused on Wnts, beta-catenin, and their receptors. Here, we sought to determine the role of Wnt antagonists in regulating hepatic differentiation of fetal liver-derived HPCs. Using mouse liver tissues derived from embryonic day E12.5 to postnatal day (PD) 28, we found that 13 of the 19 Wnt genes and almost all of Wnt receptors/co-receptors were expressed in most stages. However, Wnt antagonists SFRP2, SFRP3, and Dkk2 were only detected in the early stages. We established and characterized the reversible stable HPCs derived from E14.5 mouse fetal liver (HP14.5). HP14.5 cells were shown to express high levels of early liver progenitor cell markers, but low levels or none of late liver markers. HP14.5 cells were shown to differentiate into mature hepatocytes upon dexamethasone (Dex) stimulation. Dex-induced late marker expression and albumin promoter activity in HP14.5 cells were inhibited by exogenous expression of SFRP3. Furthermore, Dex-induced glycogen synthesis of PAS-positive HP14.5 cells was significantly inhibited by SFRP3. Therefore, our results have demonstrated that the expression of Wnt antagonists decreases as hepatic differentiation progresses, suggesting that a balanced Wnt signaling may be critical during mouse liver development and hepatic differentiation.
Bi
Yang
Y
Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China.
Huang
Jiayi
J
He
Yun
Y
Zhu
Gao-Hui
GH
Su
Yuxi
Y
He
Bai-Cheng
BC
Luo
Jinyong
J
Wang
Yi
Y
Kang
Quan
Q
Luo
Qing
Q
Chen
Liang
L
Zuo
Guo-Wei
GW
Jiang
Wei
W
Liu
Bo
B
Shi
Qiong
Q
Tang
Min
M
Zhang
Bing-Qiang
BQ
Weng
Yaguang
Y
Huang
Ailong
A
Zhou
Lan
L
Feng
Tao
T
Luu
Hue H
HH
Haydon
Rex C
RC
He
Tong-Chuan
TC
Tang
Ni
N
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000099274:Frizzled-Related Proteins
D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins