2. Academic Validation
  3. Iron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids-Epigenetic Circuit

Iron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids-Epigenetic Circuit

  • Stem Cells. 2019 Apr;37(4):489-503. doi: 10.1002/stem.2967.
Zhenbo Han 1,  Ying Yu 1,  Juan Xu 2,  Zhengyi Bao 1,  Zihang Xu 1,  Jiancheng Hu 3,  Meixi Yu 1,  Djibril Bamba 1,  Wenya Ma 1,  Fengzhi Ding 1,  Lai Zhang 1,  Mengyu Jin 1,  Gege Yan 1,  Qi Huang 1,  Xiuxiu Wang 1,  Bingjie Hua 1,  Fan Yang 1,  Yuan Li 1,  Lei Lei 4,  Nan Cao 5 6,  Zhenwei Pan 1,  Benzhi Cai 1
Affiliations

Affiliations

  • 1 Department of Pharmacy at the Second Affiliated Hospital, and Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin, People's Republic of China.
  • 2 Department of Bioinformatics, Harbin Medical University, Harbin, People's Republic of China.
  • 3 Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore, Singapore.
  • 4 Department of Histology and Embryology, Harbin Medical University, Harbin, People's Republic of China.
  • 5 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
  • 6 The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China.
PMID: 30599084 DOI: 10.1002/stem.2967
Abstract

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.

Keywords

Differentiation; H3K27me3; Iron homeostasis; NANOG; Pluripotent stem cells.

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