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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2409-2417.
Prepublished online as a Blood First Edition Paper on November 21, 2007; DOI 10.1182/blood-2007-08-107581.


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RED CELLS

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

Kathleen E. McGrath1, Paul D. Kingsley1, Anne D. Koniski1, Rebecca L. Porter1, Timothy P. Bushnell1, and James Palis1

1 University of Rochester Medical Center, Department of Pediatrics, Center for Pediatric Biomedical Research, NY

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 {alpha}4 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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Proc. Natl. Acad. Sci. USAHome page
J. Isern, S. T. Fraser, Z. He, and M. H. Baron
The fetal liver is a niche for maturation of primitive erythroid cells
PNAS, May 6, 2008; 105(18): 6662 - 6667.
[Abstract] [Full Text] [PDF]



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