Stochastic expression of fetal hemoglobin in adult erythroid cells.

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Abstract
The expression of fetal Hb, Hb F, in adult cells is cellularly restricted both in vivo and in culture. In cultures of erythroid progenitors, subclones that express or fail to express Hb F are derived from the same erythroid stem cell, a mechanism must exist whereby Hb F expression segregates in the progeny of erythroid progenitors during their differentiation. Mathematical analyses of experimental data are presented which suggest that expression of Hb F in human adult erythroid cells occurs on a stochastic basis. Hb F expression among the subclones of erythroid bursts (clones) in vitro was quantified by labeling subclones with fluorescent anti-Hb F antibodies. The observed data were compared with predictions from a stochastic model with the assumption that the expression of Hb F in a subclone occurs with a probability P equal to the frequency of Hb F-expressing subclones in an experiment. There was good fit between the observed and predicted data with respect to: the relative frequencies of monomorphic F+, monomorphic F-, and bimorphic F+/F- bursts, respectively; the size distributions among F+, F- and F+/F- bursts; and the proportions of subclones expressing Hb F within bimorphic F+/F- bursts. Given the hypothesis that erythroid progenitors which have an active Hb F program are less differentiated than cells which do not proceed to express Hb F, the stochastic event indicated by these analyses may be the probability that adult erythroid progenitor cells undergo terminal differentiation at an earlier stage than usual.