Stem cell emergence and hemopoietic activity are incompatible in mouse intraembryonic sites

In the mouse embryo, the generation of candidate progenitors for long-lasti ng hemopoiesis has been reported in the paraaortic splanchnopleura (P-Sp) / aorta-gonad-mesonephros (AGM) region. Here, we address the following questi on: can the P-Sp/AGM environment support hemopoietic differentiation as wel l as generate stem cells, and, conversely, are other sites where hemopoieti c differentiation occurs capable of generating stem cells? Although P-Sp/AG M generates de novo hemopoietic stem cells between 9.5 and 12.5 days pose c oitus (dpc), we show here that it does not support hemopoietic differentiat ion. Among mesoderm-derived sites, spleen and omentum were shown to be colo nized by exogenous cells in the same fashion as the fetal liver. Cells colo nizing the spleen were multipotent and pursued their evolution to committed progenitors in this organ. In contrast, the omentum, which was colonized b y lymphoid-committed progenitors that did not expand, cannot be considered as a hemopoietic organ. From these data, stem cell generation appears incom patible with hemopoietic activity. At the peak of hemopoietic progenitor pr oduction in the P-Sp/AGM, between 10.5 and 11.5 dpc, multipotent cells were found at the exceptional frequency of 1 out of 12 total cells and 1 out of 4 AA4.1(+) cells. Thus. progenitors within this region constitute a pool o f undifferentiated hemopoietic cells readily accessible for characterizatio n.