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

A HIERARCHICAL STEM-CELL SYSTEM: BLOOD CELL FORmation
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multipotent
hematopoietic
stem cell
common
lymphoid precursor
multipotent
hematopoietic
progenitor
granulocyte/
macrophage
progenitor
common
myeloid
precursor
NK/T cell
precursor
macrophage
dendritic cell
precursor
monocyte
THYMUS
NK cell
T cell
B cell
macrophage
dendritic cell
neutrophil
eosinophil
basophil
mast cell
Figure 22–31 A tentative scheme
of hematopoiesis. The multipotent
stem cell normally divides infrequently
to generate either more multipotent
stem cells, which are self-renewing, or
committed progenitor cells, which are
limited in the number of times that they
can divide before differentiating to form
mature blood cells. As they go through
their divisions, the progenitors become
progressively more specialized in the
range of cell types that they can give rise
to, as indicated by the branching of this
cell-lineage diagram. In adult mammals,
all of the cells shown develop mainly in the
bone marrow—except for T lymphocytes,
which as indicated develop in the thymus,
and macrophages and osteoclasts,
which develop from blood monocytes.
Some dendritic cells may also derive from
monocytes.
platelets
megakaryocyte/
erythroid
progenitor
erythroblast
megakaryocyte
erythrocyte
STEM CELL COMMITTED PROGENITORS DIFFERENTIATED CELLS
Commitment Is a Stepwise Process
Hematopoietic stem cells do not jump directly from a multipotent state into a
commitment to just one pathway of differentiation; instead, they go through a
series of progressive restrictions. The first step, usually, is commitment to either a
myeloid or a lymphoid fate. This is thought to give rise to two kinds of progenitor
cells, one capable of generating large numbers of all the different types of myeloid
cells, and the other giving rise to large numbers of all the different types of lymphoid
cells. Further steps give rise to progenitors committed to the production of
just one cell type. The steps of commitment correlate with changes in the expression
of specific transcription regulators, needed for the production of different
subsets of blood cells.
MBoC6 m23.42/22.31
Divisions of Committed Progenitor Cells Amplify the Number of
Specialized Blood Cells
Hematopoietic progenitor cells generally become committed to a particular pathway
of differentiation long before they cease proliferating and terminally differentiate.
The committed progenitors go through many rounds of cell division to
amplify the ultimate number of cells of the given specialized type. In this way, a
single stem-cell division can lead to the production of thousands of differentiated
progeny, which explains why the number of stem cells is such a small fraction
of the total population of hematopoietic cells. For the same reason, a high rate
of blood cell production can be maintained even though the stem-cell division
rate is low. The smaller the number of division cycles that the stem cells themselves
have to undergo in the course of a lifetime, the lower the risk of generating
stem-cell mutations, which would give rise to persistent mutant clones of cells in
the body—a particular danger in the hematopoietic system where, as discussed
in Chapter 20, a relatively small accumulation of mutations can be sufficient to
cause cancer. A low rate of stem-cell division also slows the process of replicative
cell senescence (discussed in Chapter 17).