ER stress reliever enhances functionalities of in vitro cultured hepatocytes.
Stem Cell Res
; 43: 101732, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-32087526
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Hepatócitos
/
Estresse do Retículo Endoplasmático
Limite:
Humans
Idioma:
En
Revista:
Stem Cell Res
Ano de publicação:
2020
Tipo de documento:
Article