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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1433-1441.
Prepublished online as a Blood First Edition Paper on October 24, 2006; DOI 10.1182/blood-2006-06-031898.
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HEMATOPOIESIS
The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis
Joanna Tober1,
Anne Koniski1,
Kathleen E. McGrath1,2,
Radhika Vemishetti3,
Rachael Emerson1,
Karen K. L. de Mesy-Bentley4,
Richard Waugh3, and
James Palis1,2
1 Center for Pediatric Biomedical Research,
2 Department of Pediatrics,
3 Department of Biomedical Engineering, and
4 Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, NY
In the adult, platelets are derived from unipotential megakaryocyte colony-forming cells (Meg-CFCs) that arise from bipotential megakaryocyte/erythroid progenitors (MEPs). To better define the developmental origin of the megakaryocyte lineage, several aspects of megakaryopoiesis, including progenitors, maturing megakaryocytes, and circulating platelets, were examined in the murine embryo. We found that a majority of hemangioblast precursors during early gastrulation contains megakaryocyte potential. Combining progenitor assays with immunohistochemical analysis, we identified 2 waves of MEPs in the yolk sac associated with the primitive and definitive erythroid lineages. Primitive MEPs emerge at E7.25 along with megakaryocyte and primitive erythroid progenitors, indicating that primitive hematopoiesis is bilineage in nature. Subsequently, definitive MEPs expand in the yolk sac with Meg-CFCs and definitive erythroid progenitors. The first GP1bß-positive cells in the conceptus were identified in the yolk sac at E9.5, while large, highly reticulated platelets were detected in the embryonic bloodstream beginning at E10.5. At this time, the number of megakaryocyte progenitors begins to decline in the yolk sac and expand in the fetal liver. We conclude that the megakaryocyte lineage initially originates from hemangioblast precursors during early gastrulation and is closely associated both with primitive and with definitive erythroid lineages in the yolk sac prior to the transition of hematopoiesis to intraembryonic sites.

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