期刊
CELLS
卷 11, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/cells11244117
关键词
human embryonic stem cells-derived hepatocytes; hepatic polarized differentiation; hepatocyte polarity; apical membrane
类别
资金
- National Key Research and Development Program of China [2018YFA0108200, 2018YFA0108201]
- South China University of Technology [D6201880, K5180910, K5204120, D6212440, D9194290, PT31900976]
- National Natural Science Foundation of China [31900976, 32071360]
- GuangZhou Basic and Applied Basic Research Foundation [202102021141]
- China Postdoctoral Science Foundation [2020M672645]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515110940]
- Guangzhou First People's Hospital [D9194290, PT31900976]
The study found that polarized differentiation enhances the maturity and liver function of human embryonic stem cell-derived hepatocytes (hEHs), and identifies molecular targets that regulate the polarization state of hEHs.
Hepatocytes exhibit a multi-polarized state under the in vivo physiological environment, however, human embryonic stem cell-derived hepatocytes (hEHs) rarely exhibit polarity features in a two-dimensional (2D) condition. Thus, we hypothesized whether the polarized differentiation might enhance the maturity and liver function of hEHs. In this study, we obtained the polarized hEHs (phEHs) by using 2D differentiation in conjunct with employing transwell-based polarized culture. Our results showed that phEHs directionally secreted albumin, urea and bile acids, and afterward, the apical membrane and blood-bile barrier (BBIB) were identified to form in phEHs. Moreover, phEHs exhibited a higher maturity and capacitity of cellular secretory and drug metabolism than those of non-phEHs. Through transcriptome analysis, it was found that the polarized differentiation induced obvious changes in gene expression profiles of cellular adhesion and membrane transport in hEHs. Our further investigation revealed that the activation of Hippo and AMPK signaling pathways made contributions to the regulation of function and cellular polarity in phEHs, further verifying that the liver function of hEHs was closely related with their polarization state. These results not only demonstrated that the polarized differentiation enhanced the maturity and liver function of hEHs, but also identified the molecular targets that regulated the polarization state of hEHs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据