Ontogeny of erythropoiesis

Department of Pediatrics, University of Rochester Medical Center, Rochester, New York 14642, USA.
Current Opinion in Hematology (Impact Factor: 3.97). 06/2008; 15(3):155-61. DOI: 10.1097/MOH.0b013e3282f97ae1
Source: PubMed


The present study review examines the current understanding of the ontogeny of erythropoiesis with a focus on the emergence of the embryonic (primitive) erythroid lineage and on the similarities and differences between the primitive and the fetal/adult (definitive) forms of erythroid cell maturation.
Primitive erythroid precursors in the mouse embryo and cultured in vitro from human embryonic stem cells undergo 'maturational' globin switching as they differentiate terminally. The appearance of a transient population of primitive 'pyrenocytes' (extruded nuclei) in the fetal bloodstream indicates that primitive erythroblasts enucleate by nuclear extrusion. In-vitro differentiation of human embryonic stem cells recapitulates hematopoietic ontogeny reminiscent of the murine yolk sac, including overlapping waves of hemangioblast, primitive, erythroid, and definitive erythroid progenitors. Definitive erythroid potential in zebrafish embryos, like that in mice, initially arises prior to, and independent of, hematopoietic stem cell emergence in the region of the aorta. Maturation of definitive erythroid cells within macrophage islands promotes erythroblast-erythroblast and erythroblast-stromal interactions that regulate red cell output.
The study of embryonic development in several different model systems, as well as in cultured human embryonic stem cells, continues to provide important insights into the ontogeny of erythropoiesis. Contrasting the similarities and differences between primitive and definitive erythropoiesis will lead to an improved understanding of erythroblast maturation and the terminal steps of erythroid differentiation.

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Available from: James Palis
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    • "Scale bar 10 í µí¼‡m. precursors still immature enter the bloodstream as vessels are created in embryonic day 8.25 (E8.25) soon after the onset of cardiac contractions and differentiate as a semisynchronous cohort while in circulation [7] [8]. A second transient wave of " definitive " erythroid progenitors from the yolk sac also enters the bloodstream and seeds the liver of the fetus. "
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    ABSTRACT: Erythroblastic islands are a hallmark of mammalian erythropoiesis consisting of a central macrophage surrounded by and interacting closely with the maturing erythroblasts. The macrophages are thought to serve many functions such as supporting erythroblast proliferation, supplying iron for hemoglobin, promoting enucleation, and clearing the nuclear debris; moreover, inhibition of erythroblastic island formation is often detrimental to erythropoiesis. There is still much not understood about the role that macrophages and microenvironment play in erythropoiesis and insights may be gleaned from a comparative analysis with erythropoietic niches in nonmammalian vertebrates which, unlike mammals, have erythrocytes that retain their nucleus. The phylogenetic development of erythroblastic islands in mammals in which the erythrocytes are anucleate underlines the importance of the macrophage in erythroblast enucleation.
    Full-text · Article · Nov 2015
    • "During this process, erythroid progenitors including BFU-E and CFU-E are generated followed by other cells in this lineage such as normoblasts, erythroblasts, reticulocytes and finally mature erythrocytes (Moritz et al., 1997). Various factors such as EPO, testosterone, estrogen, interleukin-3, granulocyte-macrophage colony-stimulating factor and inter- leukin-9 as well as cell-cell interactions and other external factors binding cell surface receptors and triggering several signaling pathways are able to regulate this process (Shiozaki et al., 1992; Palis, 2008). Maturation, proliferation and differentiation of red blood cells (RBCs) is affected by key regulators of erythropoiesis (iron, hypoxia, stress, growth factors), bone marrow (BM) niche signaling pathways regulating homeostasis (Wnt, Hox, Notch, SCF/C-kit) and erythroid differentiation (EPO-R, Figure 1 Schematic diagram of microRNA biosyn thesis and function in human cells. "
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    ABSTRACT: MicroRNAs (miRNAs) are 19-24 nucleotide non-coding ribonucleic acids binding DNA or RNA and controlling gene expression via mRNA degradation or its transcription inhibition. Erythropoies is a multi step differentiation process of erythroid progenitors to nucleate red blood cells. Maturation, proliferation and differentiation of red blood cells is affected by erythroid factors, signaling pathways in niche of hematopoietic cells, transcription factors as well as miRNAs. Expression of different types of miRNAs during erythroid development provides a background for the study of these molecules to control erythroid differentiation and maturation as well as their use as diagnostic and prognostic markers to treat erythroid disorders like thalassemia, sickle cell disease and erythrocyte enzyme deficiencies. In this paper, with reference to biosynthesis of miRNAs, their function in normal and anemic erythropoiesis has been investigated. The target molecule of each of these miRNAs has been cited in an attempt to elucidate their role in erythropoiesis. © 2015, Higher Education Press and Springer-Verlag Berlin Heidelberg.
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    • "Definitive erythrocytes first initiate in the lateral plate mesoderm located near the pronephros at a stage that is analogous to the aorta–gonad–mesonephros stage in mammals [10] [17]. In birds and mammals, or from an aquatic environment to terrestrial life in amphibians, the hemoglobin (Hb) switching is physiologically important for inducing the change in oxygen affinity required for adaptation from an embryonic or fetal environment to an atmospheric one. "
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    ABSTRACT: The metamorphosis of anuran amphibians is induced by thyroid hormone. To study the molecular mechanisms underlying tail regression during metamorphosis, we established a cell line, XL-B4, from a tadpole tail at a premetamorphic stage in Xenopus laevis. The cells expressed myoblast markers and differentiated into myotubes in differentiation medium. XL-B4 cells expressing fluorescent proteins were transplanted into tadpole tails. At 5 days posttransplantation, fluorescence was observed in myotube-like structures, suggesting that the myoblastic cells could contribute to skeletal muscle. Exposure of thyroid hormone T3 to XL-B4 cells for several days significantly induced apoptotic cell death. We then examined an early response of gene expression, which is involved in apoptosis or myogenesis, to T3. Treatment of the cells with T3 enhanced transcription of genes for matrix metalloproteinase-9 (MMP9) and thyroid hormone receptor-β. Interestingly, the T3 treatment also enhanced myoD transcripts, but decreased the amounts of myogenin mRNA and myosin heavy chain. Importantly, we also observed up-regulation of myoD expression and down-regulation of myogenin expression in tails, but not in hind limbs, when tadpoles at a premetamorphic stage were treated with T3 for 1 day. These results suggested that T3 could not only induce apoptosis, but also attenuate myogenesis in tadpole tails during metamorphosis.
    Full-text · Article · Mar 2015 · Journal of Molecular Endocrinology
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