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Letters to Nature

Nature 386, 488-493 (3 April 1997) | doi:10.1038/386488a0; Received 30 December 1996; Accepted 30 January 1997

A common precursor for primitive erythropoiesis and definitive haematopoiesis

Marion Kennedy*†, Meri Firpo*†‡, Kyunghee Choi†‡, Charles Wall†, Scott Robertson†, Neil Kabrun† & Gordon Keller†

  1. *These authors contributed equally to this work.
  2. †The National Jewish Medical and Research Center, Denver, Colorado 80206, and the Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
  3. ‡Present addresses: DNAX, Palo Alto, California (M.F.); University of Maryland at Baltimore, Maryland, USA (K.C.).
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The generation of blood cells, haematopoiesis, in the mouse embryo begins with the development of primitive nucleated erythroid cells in the yolk sac followed by the appearance of precursors for multiple definitive haematopoietic lineages1–4. The later developing lineages arise from multipotential stem cells5,6, but the relationship of primitive erythroid cells to these other haematopoietic populations is unknown. Using an in vitro embryonic stem (ES) cell differentiation system7, we show that primitive erythrocytes and other haematopoietic lineages arise from a common multipotential precursor that develops within embryoid bodies generated from differentiated ES cells. In response to vascular endothelial growth factor and c-kit ligand these precursors give rise to colonies containing immature cells (blasts) expressing marker genes characteristic of haematopoietic precursors. Many blast colonies also expressed betaH1 and beta major globins but not Brachyury, a mesodermal marker. Kinetic analysis demonstrated that the blast colony-forming cells represent a transient population, preceding the establishment of the primitive erythroid and other lineage-restricted precursors. This precursor population may represent the earliest stage of embryonic haematopoietic commitment.