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

CELL REPROGRAMMING AND PLURIPOTENT STEM CELLS
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fetal brain or ES cells neurospheres (A) pure culture of neural stem cells (B) mixture (C) of differentiated neurons (red)
and glial cells (green); cell nuclei
are blue
dissociate cells and
culture in suspension
in medium 1
dissociate and
culture as monolayer
in medium 2
switch to
medium 3
(A) (B) (C)
for injuries of the central nervous system. For example, might it be possible to use
injected neural stem cells to replace the neurons that die in Parkinson’s disease or
to repair accidents that sever the spinal cord?
Summary
Animals vary in their capacity for regeneration. At one extreme, planarian worms
contain stem cells (neoblasts) that support continual MBoC6 m23.66/22.39 turnover of all cell types, and
an entire worm can be regenerated from practically any small body fragment or
even from a single neoblast cell. Newts can regenerate limbs and other large body
parts after amputation, but the cells remain restricted according to their origins:
muscle cells in the regenerate derive from muscle, epidermis from epidermis, and so
on. In mammals, regeneration is more limited. Nevertheless, it is becoming possible
to go beyond the natural limits of wound healing by exploiting stem-cell biology.
Thus, certain regions of the nervous system contain stem cells that support production
of neurons in these sites throughout life. Neural stem cells can be obtained from
these sites or from fetal brains, grown in culture, and then grafted back into other
sites in the brain, where they are able to generate neurons appropriate to the new
location.
Figure 22–39 Neural stem cells. Shown
are the steps leading from fetal brain tissue,
via neurospheres (A), to a pure culture of
neural stem cells (B). These stem cells can
be kept proliferating as such indefinitely,
or, through a change of medium, can be
caused to differentiate (C) into neurons
(red) and glial cells (green). Neural stem
cells with the same properties can also be
derived, via a similar series of steps, from
embryonic stem (ES) or induced pluripotent
stem (iPS) cells (discussed later in this
chapter). (Micrographs from L. Conti et al.,
PLoS Biol. 3:1594–1606, 2005.)
Cell Reprogramming and Pluripotent
Stem Cells
When cells are transplanted from one site in the mammalian body to another or
are removed from the body and maintained in culture, they remain largely faithful
to their origins. Each type of specialized cell has a memory of its developmental
history and seems fixed in its specialized fate. Some limited transformations can
certainly occur, as we saw in our account of the connective-tissue cell family, and
some stem cells can generate a variety of differentiated cell types, but the possibilities
are restricted. Each type of stem cell serves for the renewal of one particular
type of tissue, and the whole pattern of self-renewing and differentiated cells in
the adult body is amazingly stable. What, at a fundamental molecular level, is the
nature of these stable differences between cell types? Is there any way to override
the cell memory mechanisms and force a switch from one state to another that is
radically different?
We have already discussed these fundamental questions from a general standpoint
in Chapter 7. Here we consider them more closely in the context of stem-cell
biology, where there has been a recent revolution in our understanding and in
our ability to manipulate states of cell differentiation. With further research, these
advances would seem to have important practical consequences.