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

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.