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ER stress reliever enhances functionalities of in vitro cultured hepatocytes

Authors
Kim, Jeong SeongHwang, Seon InRyu, Jung LimHong, Hee SuLee, Ji-MinLee, Sang MinJin, XiongHan, ChoongseongKim, Jong-HoonHan, JaeseokLee, Man-RyulWoo, Dong-Hun
Issue Date
3월-2020
Publisher
ELSEVIER
Keywords
ER stress; Pluripotent stem cells; Hepatic cells; Differentiation; Function
Citation
STEM CELL RESEARCH, v.43
Indexed
SCIE
SCOPUS
Journal Title
STEM CELL RESEARCH
Volume
43
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/57418
DOI
10.1016/j.scr.2020.101732
ISSN
1873-5061
Abstract
Endoplasmic reticulum stress (ER stress) leads an unfolded protein response (UPR) which results in internal cellular responses such as proteostasis and protein clearance. Recently, several reports demonstrated that the ER stress in stem cells could affect their stemness and fates to differentiate into certain lineages. However, the potential for controlling differentiation and function of cells by regulating ER stress needs to be further addressed. Here, we demonstrated that relieving the ER stress in cell cultures enhances the functionalities of hPSC-derived hepatocytes and other hepatic cells to be used in various research fields. Firstly, we found that UPR genes were up-regulated during hepatic differentiation of hPSCs and treatment of ER stress reliever at the hepatic induction stage of the differentiation resulted the enhanced mature marker expressions and glycogen storage of the differentiated hepatocytes. The treatment of ER stress reliever also improved the maintenance of hepatic characteristics in long-term culture of hPSC-derived hepatocytes. Furthermore, relieving ER stress increased the hepatic marker expression and CYP3A4 activity in hepatoma cell lines and human primary hepatocytes. Taken together, our findings indicate that regulating ER stress of in vitro cultured hepatocytes might be a crucial factor for enhancing differentiation, function and maintaining hepatic identity.
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