Speaker
Description
Hematopoiesis is the process by which blood and immune cells are formed. During fetal development, hematopoietic stem cells emerge from intra-embryonic aortic hemogenic endothelium (HE). We hypothesize that fetal hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) arise separately from HE, and that fetal MPPs contribute independently to postnatal blood production. However, the specific roles of these heterogeneous populations to fetal and postnatal hematopoiesis remain unclear. We used an inducible endothelial fate-mapping approach to mark cells emerging from the HE in mice at embryonic day (E)10.5 and track their contributions to hematopoiesis across time. HE-labeling was higher in MPPs compared to HSCs, suggesting that some fetal MPPs emerge independently from HE. To evaluate this hypothesis, we developed a mathematical model of HSC emergence, labeling, and proliferation in the developing mouse fetus. Our model lends support to the theory that MPPs emerge independently from HSCs. This method enables us to study how the timing of emergence from the HE affects hematopoietic cell fate. We will then use modeling and experiments to investigate the lasting impacts of prenatal factors, such as maternal infection, on hematopoiesis.
