Polyploid megakaryocytes develop randomly from a multicompartmental system of committed progenitors.

Cumulative distributions of the number of doublings undergone by mixed megakaryocytic/erythroblastic colonies and by pure megakaryocytic colonies were determined from plasma clot cultures of bone marrow (from C57BL/6 mice) supplemented with erythropoietin. Analysis of these distributions suggests that these colonies are produced by three distinct progenitors. At days 7-14, progenitors of mixed megakaryocytic/erythroblastic colonies (BFU-ME) generate tri-exponential distributions and the mean (+/- SD) fraction of this progenitor pool ceasing to proliferate per doubling (FCP) increases stepwise from 0.07 +/- 0.06 to 0.27 +/- 0.07 and 0.73 +/- 0.07. In this interval, progenitors of pure megakaryocytic colonies (CFU-M) generate bi-exponential slopes whose FCP values are compatible with the two last slopes above. Finally, CFU-M at day 3 express only the last slope. From days 5 to 9, megakaryocytes generated by BFU-ME reach lower ploidy levels than do those generated by CFU-M. It is concluded that, in the culture system used, (i) megakaryocyte progenitors that do not switch to polyploidization mature through the three consecutive compartments indicated, (ii) each progenitor population has a probability of becoming polyploid that reflects the fraction that ceases to proliferate, (iii) the exponentially distributed mitotic reserve of progenitors is determined by the combination of maturing into the next compartment and the probabilistic switch to the pathway of polyploidization, and (iv) the ploidy distribution of megakaryocytes probably depends on the progenitor from which they originate.