Abstract
The final steps of erythropoiesis involve unique cellular processes including enucleation and reorganization of membrane proteins and the cytoskeleton to produce biconcave erythrocytes. Surprisingly this process is still poorly understood. In vitro erythropoiesis protocols currently produce reticulocytes rather than biconcave erythrocytes. In addition, immortalized lines and iPSC-derived erythroid cell suffer from low enucleation and suboptimal final maturation potential. In light of the increasing prospect to use in vitro produced erythrocytes as (personalized) transfusion products or as therapeutic delivery agents, the mechanisms driving this last step of erythropoiesis are in dire need of resolving. Here we review the elusive last steps of reticulocyte maturation with an emphasis on protein sorting during the defining steps of reticulocyte formation during enucleation and maturation.
Highlights
Production of red blood cells for transfusion can have several distinct benefits for healthcare and patient wellbeing (Douay and Andreu, 2007; Goodnough and Murphy, 2014; Shah et al, 2014; Benedetto et al, 2015)
The reduction involves the membrane protein Glycophorin A (GPA), in our recent study we showed that during reticulocyte maturation GPA expression is only changing slightly compared to mature erythrocytes (Ovchynnikova et al, 2017)
In the bone marrow erythropoiesis progresses until the enucleated reticulocyte stage, after which the reticulocytes are released into the circulation where final maturation occurs
Summary
Elina Ovchynnikova1,2†, Francesca Aglialoro1,2†, Marieke von Lindern and Emile van den Akker1,2*. The final steps of erythropoiesis involve unique cellular processes including enucleation and reorganization of membrane proteins and the cytoskeleton to produce biconcave erythrocytes. In vitro erythropoiesis protocols currently produce reticulocytes rather than biconcave erythrocytes. Immortalized lines and iPSC-derived erythroid cell suffer from low enucleation and suboptimal final maturation potential. In light of the increasing prospect to use in vitro produced erythrocytes as (personalized) transfusion products or as therapeutic delivery agents, the mechanisms driving this last step of erythropoiesis are in dire need of resolving. We review the elusive last steps of reticulocyte maturation with an emphasis on protein sorting during the defining steps of reticulocyte formation during enucleation and maturation
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