Heterogeneity of erythroid precursor cells. Hemoglobin quantitation in single clones by radioimmunoassay.

Accumulation of HbF and HbA in individual erythroid clones, or bursts, grown in culture from early human erythroid progenitor cells (BFUe, erythroid burst-forming unit) was measured using sensitive and speciiic radioimmunoassays. HbF and HbA could be quantitated simultaneously in individual bursts and total hemoglobin levels as low as several hundred picograms per burst could be measured. Bursts from fetal liver, umbilical cord blood, and adult peripheral blood were studied under comparable culture conditions in order to facilitate quantitative comparison of the amounts of HbF and HbA they had produced. Individual bursts grown from fetal liver contained an average of 95% HbF (S.D. = 5.3) by the 15th culture day and demonstrated considerable homogeneity in that all bursts contained high percentages of HbF and correspondingly little or no HbA. Bursts grown from two different umbilical cord blood samples contained an average of 69% HbF and 30% HbF by the 14th culture day. Bursts from both samples demonstrated great heterogeneity (S.D. = 25.5 and 21.0, respectively) with respect to the percentages of HbF they had synthesized. Bursts of adult origin harvested on the 15th culture day contained an average of 25% HbF while bursts harvested on the 18th culture day contained an average of 13% HbF. Bursts studied at 18 days of culture demonstrated considerably more homogeneity (S.D. = 12.8) with respect to the range of percentages of HbF they had synthesized when compared to bursts harvested on day 15 (S.D. = 19.9). Most bursts of adult origin had accumulated high percentages of HbA and corresponding low amounts of HbF. The relative production of HbF and HbA by progenitors from different sources was appropriate for the developmental age of the source; thus, this characteristic appears to be determined in vivo. Bursts grown from different sources varied in the diversity of percentages of HbF they synthesized. Umbilical cord progenitors, present during the transition from one developmental stage to another when HbF is being replaced by HbA, yielded bursts with the greatest diversity with respect to the percentages of HbF they synthesized. Populations of bursts of adult origin maturing at later