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

STEM CELLS AND Renewal IN EPITHELIAL TISSUES
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(A) ASYMMETRIC DIVISION
(B) INDEPENDENT CHOICE
localized
determinant
POSSIBLE OUTCOMES
after first division cycle
of stem cell
POSSIBLE OUTCOMES
after first division cycle
of stem cell
or
or
after second division cycle
of stem cell
after second division cycle
of stem cell
or
or
etc.
environmental factors help
determine cell fate
or
or
or
or
terminally
differentiated
cell
choice determined by asymmetry in dividing stem cell
terminally
differentiated
cell
etc.
choice determined stochastically and/or by environment
Figure 22–7 Two ways for a stem cell to produce daughters with different fates: asymmetric division and independent
choice. (A) The asymmetric-division strategy gives a clone consisting of precisely one stem cell plus a steadily increasing
number of differentiating cells, in proportion to the number of cell divisions. (B) The independent-choice strategy is more variable
in its outcome. With a choice made at random by each daughter and with a 50% probability for each one to remain a stem cell
or differentiate, there is, for example, a 25% chance at the first division that both daughters will differentiate, so that the clone
eventually goes extinct. Or, at this division or later, a preponderance of daughters may chance to retain stem-cell character,
creating a clone that persists and increases in size. With the help of some mathematics, the probability distribution of clone
sizes generated from a single stem cell at any given time can be predicted on this stochastic assumption. The observations in
the gut and elsewhere fit the stochastic independent-choice strategy, but not the asymmetric-division strategy.
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matter which of them are pushed out of the nest and condemned to differentiation
and which stay in place as stem cells for the future. In most other stem-cell
systems where the question has been examined, it appears that the fates of the
daughters of a stem cell are assigned in a similar way, independently and subject
to influence from the cells’ environment.
A Single Lgr5-expressing Cell in Culture Can Generate an Entire
Organized Crypt-Villus System
The Paneth cells themselves are progeny of the stem cells, suggesting that the
intestinal stem-cell system is in some way self-maintaining and self-organizing.
This is demonstrated in a striking way by taking single dissociated Lgr5-expressing
cells and allowing them to proliferate in culture, embedded in a cell-free matrix
rich in the basal-lamina component laminin (mimicking basal lamina). The cells
proliferate, forming at first small, round epithelial vesicles. Within a few days,
however, one or another of the cells in the vesicle, at random, begins to differentiate
as a Paneth cell. This induces its neighbors to behave as stem cells and initiates
transformation of the simple vesicle into an organized structure, or organoid
(Figure 22–8A,B). Protrusions resembling crypts grow out into the surrounding
matrix and contain Paneth cells, Lgr5-expressing stem cells, and the transit amplifying
cells derived from them; these cell types are confined to the cryptlike structures.
Terminally differentiated, nondividing absorptive cells line the other parts
of the organoid epithelium, with their microvilli facing the lumen. Goblet and
enteroendocrine cells are also present, scattered through the epithelium, and the
whole “minigut” structure, with all its cell types, grows and renews itself in much
the same way as the lining of the normal intestine.