CHARACTERIZATION OF HEMATOPOIETIC PROGENITORS FROM HUMAN YOLK SACS AND EMBRYOS

Hematopoiesis first arises in the extraembryonic yolk sac, and it is g enerally believed that yolk sac-derived stem cells migrate and seed th e fetal liver at approximately week 6 of development in humans. Recent ly, the identification at day 8.5 to 9 of multipotential stem cells in intraembryonic sites different from the liver suggests that the estab lishment of hematopoiesis might be more complex than initially believe d. In an attempt to understand initial steps of hematopoiesis during h uman ontogeny, we characterized clonogenic myeloid progenitor cells in human yolk sacs and corresponding embryos at 25 to 50 days of develop ment. Most erythroid colonies derived from the yolk sacs differed from adult marrow-derived progenitors in that they also contained cells of the granulomacrophagic lineage, suggesting that they were pluripotent and exhibited a different response to cytokines. Furthermore, a subcl ass of nonerythroid progenitors generated very large granulomacrophagi c colonies, some of which generated secondary erythroid colonies on re plating, Analysis of the distribution of progenitors revealed that in contrast to erythroid progenitors, whose numbers were equally distribu ted between the yolk sac and the embryo, 80% of the nonerythroid proge nitors were found in the embryo at stages II and III. Interestingly, a high proportion of nonerythroid progenitors (including high prolifera tive potential cells) was present in colony assays initiated with cell s remaining after the liver has been removed. These findings were vali dated in colony assays established with CD34(+) cells purified from ex traembryonic yolk sacs and intraembryonic tissues. Increased knowledge about the biology of hematopoietic stem cells early in life may help to further understanding of the mechanisms associated with the restric tion in proliferative and differentiative potential observed in the ad ult hematopoietic stem cell compartment. (C) 1995 by The American Soci ety of Hematology.