Lymphoid progenitor emergence in the murine embryo and yolk sac precedes stem cell detection

Abstract

Mammalian embryos produce several waves of hematopoietic cells before the establishment of the hematopoietic stem cell (HSC) hierarchy. These early waves of embryonic hematopoiesis present a reversed hierarchy in which hematopoietic potential is first displayed by highly specialized cells that are derived from transient uni- and bipotent progenitor cells. Hematopoiesis progresses through multilineage erythro-myeloid progenitor cells that lack self-renewal potential and, subsequently, to make distinct lymphoid progenitor cells before culminating in detectable definitive HSC. This review provides an overview of the stepwise development of embryonic hematopoiesis. We focus on recent progress in demonstrating that lymphoid lineages emerge from hemogenic endothelial cells before the presence of definitive HSC activity and discuss the implications of these findings.

FIG. 1.

Murine hematopoiesis during embryonic development. Progenitors that can give rise to the primitive erythroid lineage emerge in the yolk sac at embryonic day 7.25 (E7.25). At E8.25, definitive erythro-myeloid progenitors (EMP) can be detected in the yolk sac. At E9.0, both yolk sac and para-aortic splanchnopleure (P-Sp) contain neonatal hematopoietic stem cells (HSC) that can reconstitute sublethally myeloablated newborn animals. Before the first definitive HSC can be detected, lymphoid progenitors that can differentiate into B or T lymphocytes arise in the yolk sac and P-Sp at E9.5. Finally, definitive HSC that can reconstitute lethally irradiated adult mice can be detected in the aorto-gonad-mesonephros (AGM) region at E10.5 and later in the yolk sac and placenta at E11. Definitive HSC expand in the placenta and fetal liver and migrate to the spleen and bone marrow before birth.