Dynamic Changes in Membrane Protein Expression During Murine and Human Erythropoiesis: Resolving the Distinct Stages in Terminal Erythroid Differentiation.

Abstract 4039

Poster Board III-975

Erythropoiesis is the process by which nucleated erythroid progenitors proliferate and differentiate to generate, every second, millions of non-nucleated red cells with their unique discoid shape and membrane material properties. In the present study, we examined the time-course of appearance of individual membrane proteins during erythropoiesis to enhance our understanding of the evolution of the unique features of the red cell membrane. We found that all the major transmembrane and all the skeletal proteins in mature red blood cells, except actin, accrued progressively during terminal differentiation of murine erythroid progenitors. In marked contrast, during the same time course, accumulation of various adhesion molecules decreased. In particular, the adhesion molecule, CD44 exhibited a progressive and a dramatic 30-fold decrease from proerythroblast to reticulocyte; this enabled us to devise a new strategy for distinguishing unambiguously between erythroblasts at successive developmental stages during murine erythopoiesis. By contrast, CD71, which is routinely being used as a surface marker for this purpose, proved markedly less effective than CD44 in identifying erythroblasts at successive developmental stages. Indeed, we found that CD71 expression decreased only fourfold during terminal erythroid differentiation, and not in the progressive manner observed for CD44. A similar pattern of membrane protein expression was noted during terminal differentiation of human erythroid progenitors. These findings provide new insights into the genesis of red cell membrane function during erythroblast differentiation, and also offer a means of defining stage-specific defects in erythroid maturation in inherited and acquired red cell disorders and in bone marrow failure syndromes.