An important example of the latter is a protein called Steel or Stem Cell Factor (SCF ). This is expressed both in the bone marrow stroma (where it helps to define the stem-cell niche) and along pathways of migration, and it occurs both in a membrane-bound and a soluble form. It binds to a receptor tyrosine kinase called Kit, and it is required during development for guidance and survival not only of hematopoietic cells but also of other migratory cell types—specifically, germ cells and pigment cells.
erythropoiesis depends on the hormone erythropoietin
The best understood of the CSFs that act as hormones is the glycoprotein erythropoietin, which is produced in the kidneys and regulates erythropoiesis, the formation of red blood cells, to which we now turn.
The erythrocyte is by far the most common type of cell in the blood (see Table 22–1). When mature, it is packed full of hemoglobin and contains hardly any of the usual cell organelles. In an erythrocyte of an adult mammal, even the nucleus, endoplasmic reticulum, mitochondria, and ribosomes are absent, having been extruded from the cell in the course of its development (Figure 22–33). The erythrocyte therefore cannot grow or divide, and it has a limited life-span—about 120 days in humans or 55 days in mice. Worn-out erythrocytes are phagocytosed and digested by macrophages in the liver and spleen, which remove more than 1011
Figure 22–32 Dependence of hematopoietic stem cells on contact with stromal cells. the contact-dependent interaction between the kit receptor and its ligand is one of several signaling mechanisms thought to be involved in hematopoietic stem-cell maintenance. the real system is certainly more complex. moreover, the dependence of hematopoietic cells on contact with stromal cells cannot be absolute, since small numbers of the functional stem cells can be found free in the circulation. SCF, stem-cell factor.
Figure 22–33 A developing red blood cell (erythroblast). the cell is shown extruding its nucleus to become an immature erythrocyte (a reticulocyte), which then leaves the bone marrow and passes into the bloodstream. the reticulocyte will lose its mitochondria and ribosomes within a day or two to become a mature erythrocyte. erythrocyte clones develop in the bone marrow on the surface of a macrophage, which phagocytoses and digests the nuclei discarded by the erythroblasts.
senescent erythrocytes in each of us each day. Young erythrocytes actively protect themselves from this fate: they have a protein on their surface that binds to an inhibitory receptor on macrophages and thereby prevents their phagocytosis.
A lack of oxygen or a shortage of erythrocytes stimulates specialized cells in the kidney to synthesize and secrete increased amounts of erythropoietin into the bloodstream. The erythropoietin, in turn, boosts the production of erythrocytes. The effect is rapid: the rate of release of new erythrocytes into the bloodstream rises steeply 1–2 days after an increase in erythropoietin levels in the bloodstream. Clearly, the hormone must act on cells that are close precursors of the mature erythrocytes.
The cells that respond to erythropoietin can be identified by culturing bone marrow cells in a semisolid matrix in the presence of erythropoietin. In a few days, colonies of about 60 erythrocytes appear, each founded by a single committed erythroid progenitor cell. This progenitor depends on erythropoietin for its survival as well as its proliferation. It does not yet contain hemoglobin, and it is derived from an earlier type of committed erythroid progenitor whose survival and proliferation are governed by other factors.