![]() ![]() 1 Once circulation has begun (around E9.5 in the mouse), EryPs are free to move into the embryo proper. 24 In the mouse, erythroid progenitors (EryP colony-forming cells, or EryP-CFCs, identified in vitro) are found in the yolk sac between E7.25 and E9.0 but not at later stages in either the yolk sac or embryo proper. 24 Commitment of mesodermal progenitors to the hematopoietic and endothelial lineages begins prior to or shortly after these cells exit the primitive streak. Cells with the properties of the hemangioblast were first identified in the embryonic stem cell system 21-23 and were later shown to be present in gastrulating mouse embryos. 12, 20 This finding suggests that hemangioblasts may not be the sole source of erythroid cells at this stage and/or that local signals control cell fate decisions in the hemangioblast. 16-19 Formation of EryPs has been detected in the absence of endothelial cells in the more proximal yolk sac using confocal imaging. ![]() 13-15 Some of these genes are required for normal development of both hematopoietic and endothelial cells. 5, 9-12 These lineages were proposed to arise from a common progenitor, the hemangioblast, based on their close temporal and spatial association in the blood islands and on their shared expression of a number of genes. 7 In the yolk sac, erythroid and endothelial cells arise from mesodermal clusters to form morphologically identifiable “blood islands” 8 late in gastrulation (around E7.5). Yolk sac and fetal liver erythroid cells are derived from distinct populations of mesoderm during gastrulation. The developmental origins of EryPs are poorly defined. Unexpectedly, we find that EryPs are a stable cell population that persists through the end of gestation. This study identifies previously unrecognized synchronous developmental stages leading to the maturation of EryPs in the mouse embryo. Here, we have used this line to characterize changes in cell morphology and surface-marker expression as EryPs mature and to track EryP numbers and enucleation throughout gestation. We have generated a transgenic mouse line in which the human ϵ-globin gene promoter drives expression of green fluorescent protein exclusively within the EryP lineage. Thereafter, EryDs are also present in the bloodstream, and the 2 lineages are not easily distinguished. Our analysis of embryonic blood at different stages reveals a stepwise developmental progression within the EryP lineage from E9.5 to E12.5. The development and maturation of EryPs remain poorly defined. Two to 3 days later, small cells of the definitive erythroid lineage (EryD) begin to differentiate within the fetal liver and rapidly outnumber EryPs in the circulation. Large, nucleated EryPs begin to circulate around midgestation, when connections between yolk sac and embryonic vasculature mature. Primitive erythroblasts (EryPs) are the first hematopoietic cell type to form during mammalian embryogenesis and emerge within the blood islands of the yolk sac. ![]()
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