Increasing evidence suggests that hematopoietic stem and progenitor cells from embryonic and fetal tissues demonstrate proliferative capacities greater than cells isolated from adult hematopoietic tissues. Few studies have explored the organization of the high proliferative potential hematopoietic progenitor hierarchy in the murine yolk sac. We have demonstrated the appearance of high proliferative potential colony-forming cells (HPP-CFC) in the yolk sac as early as embryonic day 8 (E8). Yolk sac HPP-CFC colony size and differentiated cellular composition were similar to adult marrow HPP-CFC. The frequency of yolk sac HPP-CFC at E11 was greater than HPP-CFC frequency in the adult marrow. Replating of primary yolk sac HPP-CFC resulted in significantly greater HPPCFC and multipotent progenitors than replated adult marrow primary HPP-CFC. Similar results were obtained when AA4.1-expressing yolk sac and adult marrow cells that bind wheat germ agglutinin (WGA) were isolated via flow cytometry. These results support growing evidence that fetal, and perhaps embryonic, hematopoietic tissues may be excellent alternative sources of highly proliferative hematopoietic cells as targets for somatic gene therapy.
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