Concomitant changes in chromatin structure and proliferative activity in differentiating human erythroblasts

Abstract

During the passage of erythroblasts down the pathway of maturation, proliferative activity is increasingly slowed and nuclear chromatin increasingly condensed. The aim of the present study was to describe this chromatin condensation by means of textural features and to find correlations between the changes in nuclear structure and the proliferative activity. As a parameter of proliferative activity, the rate of DNA synthesis was investigated in individual cells by utilizing the technique of quantitative 14C-autoradiography. The nuclear fine structure was analyzed in the same cells, after removal of the silver grains and then staining by the Feulgen reaction, by scanning cytophotometry and the application of textural parameters as used in early cancer detection. Among several features, the skewness of the distribution of optical densities proved to be the best parameter for describing the overall morphologic progression during erythroblast maturation. It was almost completely independent of the actual stage of the cells in the cell cycle. The best correlation with the rate of DNA synthesis was found to be the Laplace-filtered optical densities, a parameter that can be interpreted as expressing the "graininess" of chromatin. Since changes in the template activity related to hemoglobinization are also associated with structural changes in chromatin, the relationship between chromatin structure and proliferative activity in erythroblasts is regarded as causal only to a limited extent.