Initiation of erythropoiesis by BFU-E cells

Abstract

Erythropoiesis is the process of red blood cell production in the bone marrow. Terminal stages of human erythropoiesis occur in multicellular structures called erythroblastic islands (EBIs). EBIs contain up to several dozen erythroid cells of varying maturities organized around a central macrophage. Immature erythroid cells, burst forming units (BFU-E) circulate in blood and home to bone marrow, where they can have limited but random movement. When BFU-Es approach a macrophage, they divide producing colony forming units-erythroid (CFU-E), which are the next stage of erythroid differentiation. CFU-Es and their immediate progeny, proerythroblasts, can self-renew, differentiate into more mature cells or die by apoptosis. The BFU-E, CFU-E, and the subsequent erythroblast stages provide normal functioning of erythropoiesis. In this work we develop a hybrid discrete-continuous model in order to describe normal erythropoiesis in the bone marrow. Cells are represented as individual objects that move, divide, differentiate, die and interact with each other. We show how BFU-E cells initiate EBIs.