Hematopoietic Stem Cell Emergence in Embryonic Life: Developmental Hematology Revisited

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Abstract
In utero, hematopoiesis takes place initially in the extraembryonic yolk sac, then switches to the liver, thymus, and, finally, bone marrow. This chronologic sequence and the fact that all blood-forming tissues but the yolk sac sustain hematopoiesis after colonization by stem cells of external origin have led to the hypothesis that the whole prenatal and postnatal blood system is founded by yolk sac-derived stem cells. Experimental data recently obtained from bird and mouse embryo models strongly suggest, however, that definitive hematopoiesis is established from an intraembryonic source of stem cells arising in the vicinity of the developing aorta. In agreement, an abundant population of CD34+ primitive hematopoietic cells has been identified in the equivalent area of the human embryo. These novel findings will contribute to our understanding of blood cell homeostasis and may help to further develop therapeutic protocols making use of fetal hematopoietic cells transplanted in utero or in postnatal life.