Open AccessIron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids‐Epigenetic Circuit
Author(s) -
Han Zhenbo,
Yu Ying,
Xu Juan,
Bao Zhengyi,
Xu Zihang,
Hu Jiancheng,
Yu Meixi,
Bamba Djibril,
Ma Wenya,
Ding Fengzhi,
Zhang Lai,
Jin Mengyu,
Yan Gege,
Huang Qi,
Wang Xiuxiu,
Hua Bingjie,
Yang Fan,
Li Yuan,
Lei Lei,
Cao Nan,
Pan Zhenwei,
Cai Benzhi
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2967
Subject(s) - biology , induced pluripotent stem cell , microbiology and biotechnology , homeobox protein nanog , stem cell , homeostasis , rex1 , cellular differentiation , programmed cell death , embryonic stem cell , apoptosis , biochemistry , gene
Iron homeostasis is crucial for a variety of biological processes, but the biological role of iron homeostasis in pluripotent stem cells (PSCs) remains largely unknown. The present study aimed to determine whether iron homeostasis is involved in maintaining the pluripotency of human PSCs (hPSCs). We found that the intracellular depletion of iron leads to a rapid downregulation of NANOG and a dramatic decrease in the self‐renewal of hPSCs as well as spontaneous and nonspecific differentiation. Moreover, long‐term depletion of iron can result in the remarkable cell death of hPSCs via apoptosis and necrosis pathways. Additionally, we found that the depletion of iron increased the activity of lipoprotein‐associated phospholipase A2 (LP‐PLA2) and the production of lysophosphatidylcholine, thereby suppressing NANOG expression by enhancer of zeste homolog 2‐mediated trimethylation of histone H3 lysine 27. Consistently, LP‐PLA2 inhibition abrogated iron depletion‐induced loss of pluripotency and differentiation. Altogether, the findings of our study demonstrates that iron homeostasis, acting through glycerophospholipid metabolic pathway, is essential for the pluripotency and survival of hPSCs. Stem Cells 2019;37:489–503