ER stress reliever enhances functionalities of in vitro cultured hepatocytes

Jeong Seong Kim, Seon In Hwang, Jung Lim Ryu, Hee Su Hong, Ji Min Lee, Sang Min Lee, Xiong Jin, Choongseong Han, Jong Hoon Kim, Jaeseok Han, Man Ryul Lee, Dong Hun Woo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number101732
JournalStem Cell Research
Volume43
DOIs
Publication statusPublished - 2020 Mar

Keywords

  • Differentiation
  • ER stress
  • Function
  • Hepatic cells
  • Pluripotent stem cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Kim, J. S., Hwang, S. I., Ryu, J. L., Hong, H. S., Lee, J. M., Lee, S. M., Jin, X., Han, C., Kim, J. H., Han, J., Lee, M. R., & Woo, D. H. (2020). ER stress reliever enhances functionalities of in vitro cultured hepatocytes. Stem Cell Research, 43, [101732]. https://doi.org/10.1016/j.scr.2020.101732