Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1248 Chapter 22: Stem Cells and Tissue Renewal
eye
Figure 22–35 The planarian worm,
Schmidtea mediterranea. (A) External
view. (B) Immunostaining with three
different antibodies, revealing the internal
anatomy. (A, courtesy of A. Sánchez
Alvarado; B, from A. Sánchez Alvarado,
BMC Biol. 10:88, 2012.)
mouth
penis
genital
pore
(A) (B) gut neurons axons and
0.2 mm
pharynx
merge
a brain, a pair of primitive eyes, a peripheral nervous system, musculature, and
excretory and reproductive organs—most of the basic body parts familiar in other
animals, although all
MBoC6
relatively
n22.108/22.35
simple by vertebrate standards and built from
about 20–25 distinct differentiated cell types. For more than a century, planarians
such as Schmidtea have intrigued biologists because of their extraordinary capacity
for regeneration: a small tissue fragment taken from almost any part of the
body will reorganize itself and grow to form a complete new animal. This property
goes with another: when the animal is starved, it gets smaller and smaller, by
reducing its cell numbers while maintaining essentially normal body proportions.
This behavior is called degrowth, and it can continue until the animal is as little
as one-twentieth or even a smaller fraction of its full size. Supplied with food, it
will grow back to full size again. Cycles of degrowth and growth can be repeated
indefinitely, without impairing survival or fertility.
Underlying this behavior is a process of continual cell turnover. Along with the
differentiated cells, which do not divide, there is a population of small, apparently
undifferentiated dividing cells called neoblasts. The neoblasts constitute about
20% of the cells in the body and are widely distributed within it; by cell division,
they serve as stem cells for the production of new differentiated cells. Differentiated
cells, meanwhile, are continually dying by apoptosis, allowing their corpses
to be phagocytosed and digested by neighboring cells. Through this cell cannibalism,
the constituents of the dying cells can be efficiently recycled. Cell birth
continues in a dynamic balance with cell death and cell cannibalism, no matter
whether the animal is fed or starved. In conditions of starvation, the balance is
evidently tilted toward cell cannibalism, and in conditions of plenty, toward cell
birth.
A high dose of x-rays halts all cell division, puts a stop to cell turnover, and
destroys the capacity for regeneration. The result is death after a delay of several
weeks. The animal can be rescued, however, by injecting into it a single neoblast
isolated from an unirradiated donor (Figure 22–36). In a certain proportion of
cases, the injected cell divides to form a clone of progeny that eventually repopulate
the entire body, creating a healthy regenerative individual with an apparently
complete set of differentiated cell types as well as dividing neoblasts. Genetic
markers prove that these are all derived from the single neoblast that was injected.
It follows that at least some neoblasts are totipotent (or at least highly pluripotent)
stem cells; that is, cells able to give rise to all (or at least almost all) of the cell types
that make up the body of a flatworm, including more neoblasts like themselves.
Some Vertebrates Can Regenerate Entire Organs
One might think that such powers of regeneration would be a prerogative of small,
simple, primitive animals. But some vertebrates, too, especially fish and amphibians,
show remarkable regenerative abilities. A newt, for example, can regenerate