Essential Cell Biology 5th edition

Stem Cells and Tissue Renewal
715
SELF-
RENEWAL
hemopoietic
stem cell
T lymphocyte
B lymphocyte
eosinophil
basophil
neutrophil
osteoclast
Figure 20–38 A hemopoietic stem cell
divides to generate more stem cells,
as well as various types of precursor
cells (not shown) that proliferate and
differentiate into the mature blood cell
types found in the circulation. Note that
monocytes give rise to both macrophages,
which are found in many tissues of the
body, and osteoclasts, which eat away bone
matrix. Megakaryocytes give rise to blood
platelets by shedding cell fragments (Movie
20.5). A large number of extracellular signal
molecules are known to act at various
points in this cell lineage to help control the
production of each cell type and to maintain
appropriate numbers of precursor cells and
stem cells.
monocyte
macrophage
platelets
megakaryocyte
red blood cell
Disorders of these signaling mechanisms disrupt the structure of the
gut lining. In particular, as we see later, defects in the regulation of Wnt
signaling underlie colorectal cancer—the commonest forms of human
intestinal cancer.
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Stem Cells Can Be Used to Repair Lost or Damaged
Tissues
Because stem cells can proliferate indefinitely and produce progeny that
differentiate, they provide for both continual renewal of normal tissue
and repair of tissue lost through injury. For example, by transfusing a few
hemopoietic stem cells into a mouse whose own blood stem cells have
been destroyed by irradiation, it is possible to fully repopulate the animal
with new blood cells and ultimately rescue it from death by anemia,
infection, or both. A similar approach is used in the treatment of human
leukemia with irradiation (or cytotoxic drugs) followed by bone marrow
transplantation.
Although stem cells taken directly from adult tissues such as bone marrow
have already proven their clinical value, another type of stem cell,
first identified through experiments in mice, may have even greater potential—both
for treating and understanding human disease. It is possible,
through cell culture, to derive from early mouse embryos an extraordinary
class of stem cells called embryonic stem cells, or ES cells. Under
appropriate conditions, these cells can be kept proliferating indefinitely
in culture and yet retain unrestricted developmental potential, and are
thus said to be pluripotent: if the cells from the culture dish are put back
into an early embryo, they can give rise to all the tissues and cell types in
the body, including the reproductive germ-line cells. Their descendants
in the embryo are able to integrate perfectly into whatever site they come
to occupy, adopting the character and behavior that normal cells would
show at that site. Such an approach can be used to study gene function:
in this case, the ES cells are genetically manipulated—to inactivate a
gene or insert a modified one—prior to being returned to an embryo (see
cell
movement
absorptive cell
stem cell
secretory cell
Paneth cell
Wnt
pathway
inactive:
no cell
proliferation
Wnt pathway
active: cell
proliferation
Figure 20–39 The Wnt signaling pathway
maintains the proliferation of the stem
cells and precursor cells in the intestinal
crypt. The Wnt proteins are secreted
by cells in and around the crypt base,
especially by the Paneth cells—a subclass
of terminally differentiated secretory cells
that are generated from the gut stem cells.
Newly formed Paneth cells, which move
down to the crypt bottom instead of up to
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the tip of the villus, have a dual function:
they secrete antimicrobial peptides to keep
infection at bay, and at the same time they
provide the signals to sustain the stem-cell
population.