All blood cells arise from a type of cell called the
hematopoietic stem cell (HSC). Stem cells are cells that can differentiate into
other cell types; they are self-renewing—they maintain their population level
by cell division. In humans, hematopoiesis, the formation and development of
red and white blood cells, begins in the embryonic yolk sac during the first
weeks of development. Here, yolk-sac stem cells differentiate into primitive
erythroid cells that contain embryonic hemoglobin. In the third month of
gestation, hematopoietic stem cells migrate from the yolk sac to the fetal
liver and then to the spleen; these two organs have major roles in
hematopoiesis from the third to the seventh months of gestation. After that,
the differentiation of HSCs in the bone marrow becomes the major factor in
hematopoiesis, and by birth there is little or no hematopoiesis in the liver
and spleen.
It is remarkable that every functionally specialized, mature
blood cell is derived from the same type of stem cell. In contrast to a
unipotent cell, which differentiates into a single cell type, a hematopoietic
stem cell is multipotent, or pluripotent, able to differentiate in various ways
and thereby generate erythrocytes, granulocytes, monocytes, mast cells, lymphocytes,
and megakaryocytes. These stem cells are few, normally fewer than one HSC per 5
104 cells in the bone marrow.
The study of hematopoietic stem cells is difficult both
because of their scarcity and because they are hard to grow in vitro. As a result,
little is known about how their proliferation and differentiation are
regulated. By virtue of their capacity for self-renewal, hematopoietic stem
cells are maintained at stable levels throughout adult life; however, when
there is an increased demand for hematopoiesis, HSCs display an enormous
proliferative capacity. This can be demonstrated in mice whose hematopoietic
systems have been completely destroyed by a lethal dose of x-rays (950 rads;
one rad represents the absorption by an irradiated target of an amount of
radiation corresponding to 100 ergs/gram of target). Such irradiated mice will
die within 10 days unless they are infused with normal bone-marrow cells from a
syngeneic (genetically identical) mouse. Although a normal mouse has 3 108
bone-marrow cells, infusion of only 104 –105 bone-marrow cells (i.e.,
0.01%–0.1% of the normal amount) from a donor is sufficient to completely
restore the hematopoietic system, which demonstrates the enormous proliferative
and differentiative capacity of the stem cells.
Early in hematopoiesis, a multipotent stem cell
differentiates along one of two pathways, giving rise to either a common
lymphoid progenitor cell or a common myeloid progenitor cell (Figure 2-1). The
types and amounts of growth factors in the microenvironment of a particular
stem cell or progenitor cell control its differentiation. During the
development of the lymphoid and myeloid lineages, stem cells differentiate into
progenitor cells, which have lost the capacity for self-renewal and are committed
to a particular cell lineage. Common lymphoid progenitor cells give rise to B,
T, and NK (natural killer) cells and some dendritic cells. Myeloid stem cells
generate progenitors of red blood cells (erythrocytes), many of the various
white blood cells (neutrophils, eosinophils, basophils, monocytes, mast cells,
dendritic cells), and platelets. Progenitor commitment depends on the
acquisition of responsiveness to particular growth factors and cytokines. When
the appropriate factors and cytokines are present, progenitor cells proliferate
and differentiate into the corresponding cell type, either a mature
erythrocyte, a particular type of leukocyte, or a platelet-generating cell (the
megakaryocyte). Red and white blood cells pass into bonemarrow channels, from
which they enter the circulation.
In bone marrow, hematopoietic cells grow and mature on a
meshwork of stromal cells, which are nonhematopoietic cells that support the
growth and differentiation of hematopoietic cells. Stromal cells include fat cells,
endothelial cells, fibroblasts, and macrophages. Stromal cells influence the
differentiation of hematopoietic stem cells by providing a
hematopoietic-inducing microenvironment (HIM) consisting of a cellular matrix
and factors that promote growth and differentiation. Many of these
hematopoietic growth factors are soluble agents that arrive at their target
cells by diffusion, others are membrane-bound molecules on the surface of
stromal cells that require cell-to-cell contact between the responding cells
and the stromal cells. During infection, hematopoiesis is stimulated by the
production of hematopoietic growth factors by activated macrophages and T cells
Source : Richard A. Goldsby, Thomas J. Kindt, And Barbara A. Osborne. 2000. KUBY IMMUNOLOGY. New York. W. H. FREEMAN AND COMPANY. Page 24 - 26.
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