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Contrary to
accepted ideas, scientists from the Max Planck Institute of
Immunobiology and the University of Freiburg have found that
blood stem cells from adult mice can survive in the very
different environment of the early embryo and even go on to
produce blood cells reprogrammed to have embryonic features (Cell,
June 12, 1998).
The different red and white cell types in the blood are
generated from a cascade of progenitor cells which are first
multipotent but, with progressive differentiation, lose this
potential and are finally restricted to only one cell
lineage. At the top of this hierarchy is the so-called blood
or hematopoietic stem cell (HSC). HSCs are very special
cells: one such cell cannot only generate all the different
blood cell types of an animal, it also produces more stem
cells, so that a single HSC could repopulate the whole blood
system. In the adult mouse, blood stem cells reside in the
bone marrow but during embryonic development, they are found
in the yolk sac and fetal liver. Each developmental stage
produces specific blood cell types to serve its needs, e.g.
embryos make red blood cells specialized for the task of
obtaining oxygen from the maternal circulation. It is
generally accepted that stem cells gradually become specified
during development and that these differentiation steps are
irreversible after a certain point.
How do stem cells regulate the production of embryonic- or
adult-type blood cells? Is there a developmental clock
ticking in the progenitor cells which first tells the stem
cells to behave as embryonic, then as fetal and finally as
adult cells or is the changing microenvironment providing the
stage-specific signals to the cells? On the basis of various
experimental procedures, scientists had previously assumed
that these cells were irrevocably programmed to a specific
fate, namely to produce embryonic or adult-type white and red
blood cells. Now a team of young researchers in Freiburg,
Germany, has taken a fresh look at this. Using a combination
of two advanced techniques, cell sorting to purify the least
differentiated kind of adult blood precursor cells and then
placing them in the very early environment, the mouse
blastocyst, they have discovered an unexpected plasticity in
the programming of blood cell development.
The first surprise was that the injected adult cells survive
in the very different environment of the earliest stage of
embryonic development, the so-called blastocyst, at the
opposite end of the life cycle, with its own array of growth
factors, hormones, and other powerful stimuli. The second,
exciting aspect of the results so far obtained with this
conceptually simple but technically exceedingly difficult
system is that the adult cells now give rise to red blood
cells with embryonic features, as measured by probing for the
expression of genes specifically used only in embryonic or
adult cells. Conversely, when embryonic and fetal blood stem
cells were injected into adults, they produced adult-type
cells. Thus, the microenvironment dictates which features
stem cells express.
Now, the next question to be asked will be whether the
injected adult-type stem cells are themselves converted to
embryonic-type stem cells or merely produce more
differentiated embryonic blood cells in such mixed or
chimeric embryos. Many additional experiments are now
possible, like the analysis of the migration routes of stem
cells in the developing embryo to the various blood-producing
organs such as the liver and bone marrow. And the door is now
open for experiments to look for the molecules present in the
early embryo acting on the injected stem cells. Understanding
how stem cells regulate their behavior is important in the
field of medicine for improving hematopoietic cell
transplantations.
This research is being supported by the Max Planck Society for the Advancement of Science and the German Research Association (DFG).
Journal
Cell