Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells.
Human induced pluripotent stem (iPS) cells are similar to embryonic stem (ES) cells, and can proliferate intensively and differentiate into a variety of cell types. However, the hepatic differentiation of human iPS cells has not yet been reported. In this report, human iPS cells were induced to differentiate into hepatic cells by a stepwise protocol. The expression of liver cell markers and liver-related functions of the human iPS cell-derived cells were monitored and compared with that of differentiated human ES cells and primary human hepatocytes. Approximately 60% of the differentiated human iPS cells at day 7 expressed hepatic markers alpha fetoprotein and Alb. The differentiated cells at day 21 exhibited liver cell functions including albumin Asecretion, glycogen synthesis, urea production and inducible cytochrome P450 activity. The expression of hepatic markers and liver-related functions of the iPS cell-derived hepatic cells were comparable to that of the human ES cell-derived hepatic cells. These results show that human iPS cells, which are similar to human ES cells, can be efficiently induced to differentiate into hepatocyte-like cells.
Song
Zhihua
Z
The MOE Key Laboratory of Cell Proliferation and Differentiation, Department of cell biology, College of Life Sciences, Box 38, Peking University, Beijing 100871, China.
Cai
Jun
J
Liu
Yanxia
Y
Zhao
Dongxin
D
Yong
Jun
J
Duo
Shuguang
S
Song
Xijun
X
Guo
Yushan
Y
Zhao
Yang
Y
Qin
Han
H
Yin
Xiaolei
X
Wu
Chen
C
Che
Jie
J
Lu
Shichun
S
Ding
Mingxiao
M
Deng
Hongkui
H
D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008112:Liver Glycogen / Q000096:biosynthesis; D012709:Serum Albumin / Q000378:metabolism; D000075462:Serum Albumin, Human; D014508:Urea / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000096:biosynthesis
C422455:ALB protein, human; D006023:Glycoproteins; D008112:Liver Glycogen; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D014508:Urea; D003577:Cytochrome P-450 Enzyme System; D000075462:Serum Albumin, Human