Erythroblast enucleation

Abstract

E rythrocytes, commonly called red cells, are the cellular elements of blood that perform the unique function of ensuring proper oxygen delivery to the tissues. 1 The average blood volume for an adult is 5 liters (55-75 mL/Kg of body weight) and the blood contains approximately 10 9 red cells per milliliter. Red cells do not normally contain a nucleus and are unable to proliferate. They have a limited life-span (~120 days in humans) and are replenished by the constant generation of new cells from hematopoietic stem/progenitor cell compartments. The process of erythropoiesis includes two phases: a first commitment/proliferation phase in which stem/progenitor cells are induced by extrinsic (growth factors) and intrinsic (transcription factors) factors to expand and to activate the differentiation programs and a second maturation phase in which the first morphologically recognizable erythroid cell (the pro-erythroblast) becomes unable to proliferate and undergoes cytoplasmic and nuclear alterations. Cytoplasmic maturation includes loss of mitochondria, reduction of ribosome numbers and reorganization of the microfilament structure and is mediated by the autophagic program, a proteosome-dependent pathway of proteolysis developed by eukaryotic cells to survive starvation (but which may lead to death).2 Nuclear changes involve chromosome condensation and loss of cytoplasmic-nuclear junctions in preparation for enucleation and may represent an extreme case of asymmetric division (Figure 1). The enucleation processThe earliest recognizable erythroid cell, the pro-erythroblast, undergoes four or five mitotic divisions which generate, in sequence, basophilic, polychromatophilic and orthochromatic erythroblasts ( Figure 2A). The morphological differences between these cells reflect progressive accumulation of hemoglobin (and other erythroid-specific proteins) and decrease in nuclear size and activity.1 The nucleus becomes dense, because of chromosome condensation, is isolated from the cytoplasm by a ring of cytoplasmic membranes and moves to one side of the cell. 3 The orthochromatic erythroblast is then partitioned into two daughter structures, the reticulocyte, containing most of the cytoplasm, and the pyrenocyte, containing the condensed nucleus encased in a thin cytoplasmic layer. This partitioning is called nuclear extrusion or enucleation and is favored by interaction between the erythroblasts and the macrophage within the erythroid niche, an anatomical structure first identified by Bessis in 1958 4 (Figure 1). Since most of the pyrenocytes are engulfed and degraded by the macrophage, 3 their recognition as bona fide cells occurred when they were discovered in the blood of embryos (which contains limited numbers of macrophages) where they are released during the enucleation process of primitive mammalian erythroblasts. 5Enucleated erythrocytes are present in the blood of all mammals, suggesting that enucleation provides an evolutionary advantage. Studies in lower eukaryotes (budding yeast and Drosophila) are clarifyi...

Regulation of murine normal and stress-induced erythropoiesis by Desert Hedgehog

“…At the later erythroblast stages, the nucleus progressively shrinks and is shed before the cells become mature erythrocytes. 38 The developmental program from HSCs to mature erythrocyte is regulated by complex transcriptional networks and by environmental signals. 39,40 In the adult, most erythropoiesis occurs in the BM, but under conditions of erythropoietic stress (anemia, hypoxia), the number of erythrocytes is increased, and this process of stress-induced erythropoiesis occurs predominantly in the spleen.…”

Circular RNA enrichment in platelets is a signature of transcriptome degradation

“…2 Unlike anucleate erythrocytes, which have a lifespan of ;4 months and have greatly reduced ribosome numbers, 3 platelets are short lived (;8-11 days 4 ) and translationally competent, 5 and a number of genes have been shown to undergo cytoplasmic splicing on platelet activation. 6,7 Consistent with these observations, recent RNAseq analyses have defined a complex platelet transcriptome.…”

Single-cell Transcriptomic Landscape of Nucleated Cells in Umbilical Cord Blood

“…In mammal hematopoiesis, nucleated red blood cells (NRBCs) precursors, or erythroblast, undergo several developmental stages in the bone marrow and progressively decrease cellular volume and RNA content, while accumulating specific functional proteins such as hemoglobin[16, 17]. It has been known for decades that erythroblast exist in relative large numbers in cord blood[18-20].…”