Iron overload inhibits self-renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species

Zhenbo Han; Zihang Xu; Lei Chen; Danyu Ye; Yang Yu; Ying Zhang; Yang Cao; Bamba Djibril; Xiaofei Guo; Xinlu Gao; Wenwen Zhang; Meixi Yu; Shenzhen Liu; Gege Yan; Mengyu Jin; Qi Huang; Xiuxiu Wang; Bingjie Hua; Chao Feng; Fan Yang; Wenya Ma; Yu Liu

doi:10.1002/2211-5463.12811

Iron overload inhibits self-renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species

FEBS Open Bio. 2020 May;10(5):726-733. doi: 10.1002/2211-5463.12811. Epub 2020 Apr 7.

Authors

Zhenbo Han^{1

2}, Zihang Xu^{1

2}, Lei Chen³, Danyu Ye^{1

2}, Yang Yu^{1

2}, Ying Zhang^{1

2}, Yang Cao^{1

2}, Bamba Djibril^{1

2}, Xiaofei Guo^{1

2}, Xinlu Gao^{1

2}, Wenwen Zhang^{1

2}, Meixi Yu^{1

2}, Shenzhen Liu^{1

2}, Gege Yan^{1

2}, Mengyu Jin^{1

2}, Qi Huang^{1

2}, Xiuxiu Wang^{1

2}, Bingjie Hua^{1

2}, Chao Feng^{1

2}, Fan Yang^{1

2}, Wenya Ma^{1

2}, Yu Liu⁴

Affiliations

¹ Department of Pharmacy, The Affiliated Second Hospital, Harbin Medical University, Harbin, China.
² Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.
³ Beijing Ruihua Heart Rehabilitation Research Center, China.
⁴ Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, China.

Abstract

Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ferric ammonium citrate (FAC) in a concentration-dependent manner. In addition, deferoxamine protected hESCs/hiPSCs against FAC-induced cell-cycle arrest. However, iron overload did not affect pluripotency in hESCs/hiPSCs. Further, treatment of hiPSCs with FAC resulted in excess reactive oxygen species production and DNA damage. Collectively, our findings provide new insights into the role of iron homeostasis in the maintenance of self-renewal in human pluripotent stem cells.

Keywords: DNA damage; ROS; cell cycle; human embryonic stem cells; human induced pluripotent stem cells; iron overload.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Cell Cycle / drug effects
Cell Proliferation / drug effects
DNA Damage / drug effects
Deferoxamine / pharmacology
Ferric Compounds / adverse effects
Ferric Compounds / pharmacology
Humans
Induced Pluripotent Stem Cells / drug effects
Induced Pluripotent Stem Cells / metabolism
Iron / adverse effects
Iron / metabolism
Iron Overload / metabolism*
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / metabolism
Oxidative Stress / drug effects
Pluripotent Stem Cells / drug effects*
Pluripotent Stem Cells / metabolism
Quaternary Ammonium Compounds / adverse effects
Quaternary Ammonium Compounds / pharmacology
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects

Substances

Ferric Compounds
Quaternary Ammonium Compounds
Reactive Oxygen Species
Iron
Deferoxamine
ferric ammonium citrate