From stem cell to erythroblast: regulation of red cell production at multiple levels by multiple hormones

Abstract

This article reviews the regulation of production of red blood cells at several levels: (1) the ability of erythropoietin and adhesion to a fibronectin matrix to stimulate the rapid production of red cells by inducing terminal proliferation and differentiation of committed erythroid CFU-E progenitors; (2) the regulated expansion of the pool of earlier BFU-E erythroid progenitors by glucocorticoids and other factors that occurs during chronic anemia or inflammation; and (3) the expansion of thehematopoietic cell pool to produce more progenitors of all hematopoietic lineages.

FIGURE 1. Formation of blood cells from hematopoietic stem cells in the bone marrow

Pluripotent long- term reconstituting stem cells may divide symmetrically to self-renew or divide asymmetrically to form a myeloid or lymphoid progenitor cell and a daughter cell that is pluripotent like the parental stem cell. Depending on the types and amounts of cytokines present, the myeloid and lymphoid progenitor cells undergo rapid rounds of cell division and generate different types of unipotent precursor cells, which are incapable of self-renewal. Unipotent precursor cells respond to one or a few specific cytokines, and are detected by their ability to form colonies containing the differentiated cell types shown at right, measured as colony-forming units (CFU-s). (Adapted from (33)).