The chorio-allantoic placenta provides for the exchange of nutrients, gas, and waste between the fetus and mother. The murine placenta is also enriched for long term repopulating hematopoietic stem cells, and is therefore a stem cell niche (

Gekas et al. Dev. Cell 8, 365, 2005
and
Ottersbach et al. Dev. Cell 8, 377, 2005
). However, it is not known if the placenta is colonized by hematopoietic stem cells that originate from other sites in the conceptus, or whether the placenta itself is also a site of hematopoietic cell emergence. The placenta is formed through the fusion of the allantois, a mesodermal extension from the primitive streak, with the chorionic plate, which is comprised of extraembryonic ectoderm and mesoderm. Here we show that the allantois and chorion, isolated before chorio-allantoic fusion and prior to the establishment of circulation, contain hematopoietic potential. Both allantois and chorion explants produced CD45 positive cells, some of which also expressed Mac-1 and Gr-1, when cultured on OP9 stromal cells in the presence of cytokines that promote myeloid cell differentiation. Cultures of allantois and chorion explants in the presence of lymphoid promoting cytokines induced B220 and CD19 positive B cells. Spatial and temporal analysis of Runx1, a marker for definitive hematopoiesis, showed Runx1 is not expressed in either the allantois or the chorion prior to fusion, but is expressed at the base of the allantois and at the chorio-allantoic junction following fusion. Both allantoic explant cultures, and cultures of whole embryos from which allantoises were removed in order to prohibit chorio-allantoic fusion showed that Runx1 expression in neither tissue is dependent upon fusion. We conclude that the allantois and chorion have intrinsic hematopoietic potential prior to the establishment of circulation. Our results furthermore suggest that the placenta is both a niche and a source of hematopoietic cells.

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