Enucleation of primitive erythroid cells generates a transient population of "pyrenocytes" in the mammalian fetus

University of Rochester Medical Center, Department of Pediatrics, Center for Pediatric Biomedical Research, Rochester, NY 14642, USA.
Blood (Impact Factor: 10.43). 03/2008; 111(4):2409-17. DOI: 10.1182/blood-2007-08-107581
Source: PubMed

ABSTRACT Enucleation is the hallmark of erythropoiesis in mammals. Previously, we determined that yolk sac-derived primitive erythroblasts mature in the bloodstream and enucleate between embryonic day (E)14.5 and E16.5 of mouse gestation. While definitive erythroblasts enucleate by nuclear extrusion, generating reticulocytes and small, nucleated cells with a thin rim of cytoplasm ("pyrenocytes"), it is unclear by what mechanism primitive erythroblasts enucleate. Immunohistochemical examination of fetal blood revealed primitive pyrenocytes that were confirmed by multispectral imaging flow cytometry to constitute a distinct, transient cell population. The frequency of primitive erythroblasts was higher in the liver than the bloodstream, suggesting that they enucleate in the liver, a possibility supported by their proximity to liver macrophages and the isolation of erythroblast islands containing primitive erythroblasts. Furthermore, primitive erythroblasts can reconstitute erythroblast islands in vitro by attaching to fetal liver-derived macrophages, an association mediated in part by alpha4 integrin. Late-stage primitive erythroblasts fail to enucleate in vitro unless cocultured with macrophage cells. Our studies indicate that primitive erythroblasts enucleate by nuclear extrusion to generate erythrocytes and pyrenocytes and suggest this occurs in the fetal liver in association with macrophages. Continued studies comparing primitive and definitive erythropoiesis will lead to an improved understanding of terminal erythroid maturation.

  • Source
    • "Erythroblastic islands have been described during primitive erythropoiesis as well. Even though erythroblasts in the yolk sac do not require a specialized microenvironment for development, they attach closely to structures highly similar to erythroblastic islands (McGrath et al., 2008). Moreover, erythroblastic islands have been reported in other sites for definitive erythropoiesis such as fetal liver and splenic red pulp (Manwani and Bieker, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Macrophages tightly control the production and clearance of red blood cells (RBC). During steady state hematopoiesis, approximately 10(10) RBC are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages.
    Frontiers in Physiology 01/2014; 5:9. DOI:10.3389/fphys.2014.00009 · 3.50 Impact Factor
  • Source
    • "After exiting the final cell cycle, the nuclei of orthochromatic erythroblasts are polarized to one side of the cell. Eventually these cells enucleate to form reticulocyte and a " pyrenocyte, " the extruded nucleus with a thin rim of cytoplasm surrounded by a plasma membrane [10] [23]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Even though the production of orthochromatic erythroblasts can be scaled up to fulfill clinical requirements, enucleation remains one of the critical rate-limiting steps in the production of transfusable red blood cells. Mammalian erythrocytes extrude their nucleus prior to entering circulation, likely to impart flexibility and improve the ability to traverse through capillaries that are half the size of erythrocytes. Recently, there have been many advances in our understanding of the mechanisms underlying mammalian erythrocyte enucleation. This review summarizes these advances, discusses the possible future directions in the field, and evaluates the prospects for improved ex vivo production of red blood cells.
    10/2011; 2011:139851. DOI:10.4061/2011/139851
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this work is to present a methodology aimed at valuation and hedging of basket credit derivatives, as well as of portfolios of credits/loans, in the context of several possible credit ratings of underlying credit instruments. The methodology is based on a specific Markovian model of a financial market.
Show more