Identification and Characterization of Three Classes of Erythroid Progenitors in Human Fetal Liver

Abstract

AbstractErythroid progenitors from 18 fetal livers (7–15-wk gestational period) and 13 normal adult marrows were grown in methylcellulose cultures containing erythropoietin (Ep) and burst-enhancing factor(s) (BEF). Additional experiments were carried out on 1 fetal, 15 neonatal, and 26 adult blood specimens. Three classes of progenitors (primitive or mature erythroid burst-forming unit(s), P-BFU-E, M-BFU-E respectively; erythroid colony-forming unit(s), CFU-E) have been identified in fetal liver. Identification was based on their differential clonogenic characteristics (i.e., colony morphology and number, time/growth curve, Ep and BEF sensitivity, in vitro 3H-thymidine suicide index). The multistep differentiation of fetal erythroid progenitors is associated with: (1) gradual amplification of their pool size, (2) progressive decline of their BEF response, (3) gradual enhancement of their Ep sensitivity. Marked differences are observed, however, between the characteristics of corresponding fetal and adult erythroid progenitors. Thus: (1) Differentiation of adult precursors entails a gradual increase of their proliferative rate, while all fetal progenitors are characterized by maximal cycling activity. The doubling time of cells in fetal bursts is distinctly lower than in adult ones, while intermediate values are observed in cord blood bursts. These observations suggest that ontogenic development is associated with a progressive decline of both (A) proliferative activity of early and intermediate erythroid progenitors, and (B) cell doubling time in erythropoietic differentiation. (2) Adherent cells apparently play a key role in BEF production in adult marrow cultures, but not in fetal liver ones. Finally, (3) the sensitivity to added Ep of fetal CFU-E and M-BFU-E is apparently more elevated than that of corresponding adult progenitors.