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First published online June 20, 2008
doi: 10.1242/10.1242/dev.021279

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The discovery of a source of adult hematopoietic cells in the embryo

¹ Erasmus MC, Erasmus Stem Cell Institute, Department of Cell Biology, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
² University of Edinburgh, MRC Centre for Regenerative Medicine/Institute for Stem Cell Research, Kings Buildings, West Mains Road, Edinburgh EH9 3JQ, UK.

View larger version (19K): [in this window] [in a new window]   Fig. 1. The avian yolk sac chimera experiment. The experimental strategy for the generation and analysis of yolk sac chimeras. An embryonic day 2 (E2) quail embryo body (blue) is used to replace a chick embryo body on the chick blastoderm (presumptive yolk sac) before the circulation is established in the host or grafted embryo. After several days of in ovo development (E4-E13), the spleen and thymus tissues are examined for a natural marker that distinguishes quail cells from chick cells. Quail cells contain a characteristically large, irregular nucleus, with a large heterochromatic mass, whereas chick cells contain finely dispersed heterochromatin. The results show that the progeny of cells derived from the quail embryo body (and not the chick yolk sac) contribute to the hematopoietic cell population in these adult tissues.

View larger version (14K): [in this window] [in a new window]   Fig. 2. Principle scenarios for vertebrate hematopoietic development. A schematic representation of hematopoietic system generation during embryonic development. (A) Prior to the avian yolk sac chimera experiments of Dieterlen-Lièvre, the hematopoietic system was thought to emerge once during development and to originate from a single cohort of mesenchymal/endothelial-type precursors or hemangioblasts (stellar-like cells). Primitive erythroid cells (red punctate areas) first appear and are followed by the appearance of myeloid or mixed erythroid-myeloid hematopoietic progenitors (yellow region transiting into the region of graded red). (B) In the JEEM publication, Dieterlen-Lièvre showed that two independent waves of hematopoietic generation exist during avian development: the transitory, embryonic hematopoietic cell hierarchy coming from the yolk sac (left curve containing red-punctate and yellow regions); and the adult definitive hematopoietic cell hierarchy coming from the body of the embryo (right curve containing graded red region). The hierarchies emerge independently from at least two distinct types of embryonic precursors (indicated by two stellar cells) and overlap in developmental time. This scenario became the prevailing model in the field of developmental hematopoiesis, and was followed by the finding in mammals that immature adult-type progenitors and HSCs develop with a significant delay in the conceptus (Medvinsky and Dzierzak, 1996; Medvinsky et al., 1993; Muller et al., 1994).

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