Correlation between protein synthesis rate and nuclear morphology of human erythroblasts as determined by quantitative autoradiography and high-resolution image analysis.

Human erythropoiesis is an appropriate model for analyzing correlations between functional activity of cells during maturation and nuclear morphology as determined by high-resolution image analysis. In a previous study a relationship had been found between nuclear condensation and the proliferative activity of the cells. This present study analyzed the correlation between nuclear morphology and the protein synthesis rate. The latter was assayed by measuring the 14C-1-leucine incorporation rate utilizing the technique of quantitative 14C-autoradiography. The labeled cells were first classified according to conventional cytological criteria into four groups of increasing maturity. Following grain counting the nuclei were Feulgen-stained, and after removal of the silver grains, the local nuclear optical densities were evaluated by scanning. There was a nonlinear relationship between the protein synthesis rate and features representing the degree of chromatin condensation. This nonlinearity was explained by the mediator function of RNA, predominantly mRNA. The amount of protein produced at a given time depends on the transcriptional activity of the chromatin, the frequency of mitotic divisions partitioning the mRNA, and the half-life of the mRNA. It was concluded that the chromatin texture of erythroblasts reflects three different metabolic activities: the rate of DNA strand duplication, the transcriptional activity for structural proteins enabling a cell to grow and cycle, and for functional proteins, particularly hemoglobin. Since these three activities appear to be synchronized, it is understandable that functional as well as textural features can be used to perform a supervised classification by means of multivariate analysis. Application of the five most significant features allowed a consistent classification of the erythroblasts into the various cytological compartments in 76.7% of all cases, while the classification error of the observer amounted to 13.7%.