Identification of the emergence of clonally multipotent hematopoietic stem and progenitor populations in the mouse embryo (153.10)

Abstract

Abstract In the adult hematopoietic system, all mature blood cells derive from the hematopoietic stem cell (HSC). However, HSCs are not the first blood-forming cells to appear during embryogenesis. Rather, erythrocyte-biased progenitors can be identified in the yolk sac (YS) blood islands approximately a week after fertilization. After the establishment of circulation, fully functional HSCs can be identified within the aorta-gonad-mesonephros (AGM) and fetal liver (FL) tissues. The origin and maturation of HSCs in embryonic development remains an open and important question. To help address this issue, we sought to identify and isolate the blood-forming populations within these embryonic tissues at the stages when hematopoietic potential first appears. Using a modified OP9 stromal line that can yield 8 hematopoietic lineages (B, T, NK, DC, granulocyte, macrophage, platelet, and erythrocyte), we identified populations with multipotent potential at the clonal level in all tissues. While these embryonic multipotent cells share many of the surface markers that define adult HSCs, there are also distinct tissue-specific differences. Furthermore, these populations lack the ability to engraft into adult irradiated recipient mice, indicating their development into mature HSCs is incomplete. Our data support a model by which the ability to generate all hematopoietic lineages emerges prior to the ability to engraft.