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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.

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    • "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). "
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