Induction of enucleation in primary and immortalized erythroid cells

Enucleation is a crucial event during the erythropoiesis, implicating drastic morphologic and transcriptomic/proteomic changes. While many genes deletion lead to failed or impaired enucleation have been identified, directly triggering the erythroid maturation, particularly enucleation, is still challenging. Inducing enucleation at the desired timing is necessary to develop efficient methods to generate mature, fully functional red blood cells in vitro for future transfusion therapies. However, there are considerable differences between primary erythroid cells and cultured cell sources, particularly pluripotent stem cell-derived erythroid cells and immortalized erythroid cell lines. For instance, the difference in the proliferative status between those cell types could be a critical factor, as cell cycle exit is closely connected to the terminal maturation of primary. In this review, we will discuss previous findings on the enucleation machinery and current challengings to trigger the enucleation of infinite erythroid cell sources.