Reticulocyte Maturation

Abstract

Changes to the membrane proteins and rearrangement of the cytoskeleton must occur for a reticulocyte to mature into a red blood cell (RBC). Different mechanisms of reticulocyte maturation have been proposed to reduce the size and volume of the reticulocyte plasma membrane and to eliminate residual organelles. Lysosomal protein degradation, exosome release, autophagy and the extrusion of large autophagic–endocytic hybrid vesicles have been shown to contribute to reticulocyte maturation. These processes may occur simultaneously or perhaps sequentially. Reticulocyte maturation is incompletely understood and requires further investigation. RBCs with membrane defects or cation leak disorders caused by genetic variants offer an insight into reticulocyte maturation as they present characteristics of incomplete maturation. In this review, we compare the structure of the mature RBC membrane with that of the reticulocyte. We discuss the mechanisms of reticulocyte maturation with a focus on incomplete reticulocyte maturation in red cell variants.

Generation of red blood cells from stem cells: Achievements, opportunities and perspectives for malaria research

“…The immediate precursor to the mature biconcave erythrocyte, the term reticulocyte describes enucleated cells (of evolving maturity) that are generated following extrusion of the erythroblast condensed nucleus (pyrenocyte) and in vivo exit the bone marrow to enter the bloodstream and circulate the body, remodelling their membrane to achieve biconcavity as they do so. Although able to effectively function in the same way as the slightly more mature definitive erythrocyte, reticulocytes are larger in size, contain residual RNA (classically detectable with nucleic acid binding dyes such as thiazole orange) and retain expression of the transferrin receptor CD71 (at varying levels) that is lost progressively during maturation ( Malleret et al., 2013 ; Ovchynnikova et al., 2018 ; Stevens-Hernandez and Bruce, 2022 ).…”

Exosome mediated cell signal toward breast cancer metastasis: A comprehensive review

“…They were initially found after the removal of transferrin receptors during reticulocyte development. A large percentage of the plasma membrane was regenerated as a consequence of having a significant number of alterations near the end of this process during the transition to becoming a mature erythrocyte [12]. Because of the existence of many vesicles inside them, these molecules were dubbed multivesicular bodies, and the vesicles were renamed intraluminal endosomal vesicles, which are now known as exosomes.…”

Recent updates of stem cell-based erythropoiesis

“…Orthochromatophilic erythroblasts (8–12 µm) have a dark, opaque nucleus with gray–red cytoplasm, and the nucleus has a pyknotic morphology with abundant acidophilic hemoglobin [ 10 ]. In some cases, in the process of extrusion, the cells become reticulocytes [ 13 ]. Reticulocytes (7–10 µm) have a reddish–pale blue cytoplasm with an extruded nucleus and with RNA still present.…”