Pluripotential Hematopoietic Stem Cells, Growth Inducers, and Differentiation Inducers. The blood cells begin their lives in the bone marrow from a single type of cell called the pluripotential hematopoietic stem cell, from which all the cells of the circulating blood are eventually derived. Figure 1 shows the successive divisions of the pluripotential cells to form the different circulating blood cells. As these cells reproduce, a small portion of them remains exactly like the original pluripotential cells and is retained in the bone marrow to maintain a supply of these, although their numbers diminish with age. Most of the reproduced cells, however, differentiate to form the other cell types shown to the right in Figure 1. The intermediate-stage cells are very much like the pluripotential stem cells, even though they have already become committed to a particular line of cells and are called committed stem cells.
Fig1. Formation of the multiple different blood cells from the original pluripotent hematopoietic stem cell in the bone marrow.
The different committed stem cells, when grown in culture, will produce colonies of specific types of blood cells. A committed stem cell that produces erythrocytes is called a colony-forming unit–erythrocyte, and the abbreviation CFU-E is used to designate this type of stem cell. Likewise, colony forming units that form granulocytes and monocytes have the designation CFU GM and so forth.
Growth and reproduction of the different stem cells are controlled by multiple proteins called growth inducers. At least four major growth inducers have been described, each having different characteristics. One of these, interleukin-3, promotes growth and reproduction of virtually all the different types of committed stem cells, whereas the others induce growth of only specific types of cells.
The growth inducers promote growth but not differentiation of the cells, which is the function of another set of proteins called differentiation inducers. Each of these differentiation inducers causes one type of committed stem cell to differentiate one or more steps toward a final adult blood cell.
Formation of the growth inducers and differentiation inducers is controlled by factors outside the bone marrow. For instance, in the case of RBCs, exposure of the blood to low oxygen for a long time causes growth induction, differentiation, and production of greatly increased numbers of RBCs, as discussed later in the chapter. In the case of some of the white blood cells, infectious diseases cause growth, differentiation, and eventual formation of specific types of white blood cells that are needed to combat each infection.
