The emergence of the hematopoietic system in the mammalian embryo is characterized by two temporally overlapping waves of distinct “primitive” and “definitive” erythroid progenitors that peak in the murine yolk sac at E8.5 and E10.5, respectively. We have recently determined that each wave contains megakaryocyte potential (Tober, et al., submitted), but the initial emergence of distinct myeloid lineages is less well understood. Temporal and spatial analysis of hematopoietic progenitors in the murine embryo suggest that the macrophage lineage is associated with both waves, while neutrophil and mast cell lineages are restricted to the second, definitive wave (

Palis, et al., Development 126:5073, 1999
). To better define the emergence of myelopoiesis in the murine embryo, we cultured dissociated E9.5 yolk sac cells in a broad array of cytokines (SCF, IL3, IL5, IL6, IL7, IL9, IL11 and GM-CSF) for seven days and identified morphologically distinguishable macrophages, neutrophils, eosinophils, basophils, and mast cells. The presence of eosinophils was further confirmed by expression of eosinophil peroxidase transcripts. As expected, this multilineage myeloid potential was restricted to c-kit++ cells. However, unlike the bone marrow, these c-kit++ cells in the E9.5 yolk sac were predominately a single population that also express CD41 and Fc gamma receptor (FcγR, CD16/32). FcγR+ cells first emerge in the yolk sac between E8.5 and E9.5 and are not found in the embryo proper until E10.5, when they are restricted to the liver. These findings suggest that the expression of FcγR is restricted in the yolk sac to definitive hematopoiesis and tracks its transition to the fetal liver. While mature definitive erythroid cells first emerge from the fetal liver at E12.5, to our knowledge the onset of granulopoiesis has not been investigated in the early murine embryo. We found approximately 1000 GR1+/Mac1+ cells in the fetal liver at E12.5 and this population expands 100-fold during the next two days of development. These GR1+/Mac1+ cells consisted predominantly of progressively maturing neutrophils. We conclude that the potential to generate multiple myeloid lineages first arises in the yolk sac along with definitive erythroid progenitors and that a robust granulocyte population subsequently emerges in the fetal liver at midgestation.

Topics:
antigens, cd16, cytokine, embryo, eosinophil peroxidase, granulocyte-macrophage colony-stimulating factor, interleukin-11, interleukin-3, interleukin-5, interleukin-6, interleukin-7

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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