THE APOPTOTIC AND NONAPOPTOTIC NATURE OF THE TERMINAL DIFFERENTIATIONOF ERYTHROID-CELLS

The morphology of erythroid cells changes dramatically during the cour se of their terminal differentiation. According to calculations made w ith cytospin preparations obtained from Syrian hamster yolk-sac-derive d erythroid cells, the area of nuclei at day 10 of gestation ranges fr om 25 to 85 mu m(2) and is reduced to 15-25 mu m(2) on day 13 [K. Mori oka and R. Minamikawa-Tachino, Dev. Growth Differ. 35, 569-582, 1993]. The DNA and protein contents of each nucleus also decrease during thi s period. Nonspecific fragmentation of DNA was detected by agarose gel electrophoresis in all samples obtained from day 10 to day 13 of gest ation, while distinct ladders of DNA fragments were not detected. DNA fragmentation was also detected by an in situ DNA-end labeling (TUNEL) assay. As the terminal differentiation proceeded, gradual decreases i n levels of both histone Hi and most nonhistone proteins were observed by SDS-polyacrylamide gel electrophoresis, while levels of core histo nes appeared to be constant. In particular, lamin B-2 was almost compl etely lost from the nuclear matrix fraction on day 11, These results s uggest that the terminal differentiation of erythroid cells and apopto sis might have common mechanisms. However, expansion of the cytoplasm during the terminal differentiation distinguishes these processes. In addition, in the erythroid terminal differentiation, nuclei never form lobules or become fragmented; no apoptotic bodies are formed, occurre nce of the apoptosis-like cellular change is not sporadic but rather s ynchronous, and the process is slow, with at least several days being required for cell death. These characteristics are different from thos e of typical apoptosis. Thus, the terminal differentiation of nucleate d embryonic erythroid cells exhibits both apoptotic and nonapoptotic f eatures. (C) 1998 Academic Press.