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The Journal of Neuroscience, May 15, 2000, 20(10):3725-3735
Cell Contact Regulates Fate Choice by Cortical Stem Cells
Robert Y. L.
Tsai and
Ronald D. G.
McKay
Laboratory of Molecular Biology, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
20892
Cell fate is determined by intrinsic programs and external cues,
such as soluble signals and cell-cell contact. Previous studies have
demonstrated the roles of soluble factors in the proliferation and
differentiation of cortical stem cells and cell-cell contact in
maintaining stem cells in a proliferative state. In the present study,
we focused on the effect of cell-cell interaction on cell-fate determination. We found that density could exert a strong influence on
the cell-type composition when cortical stem cells differentiate. Multipotent stem cells, which normally gave rise to neurons,
astrocytes, and oligodendrocytes under high-density culture condition,
differentiated almost exclusively into smooth muscle at low density.
Clonal analysis indicated that smooth muscle and astrocytes were
derived from a common precursor and that the density effect on cell
types used an instructive mechanism on the choice of fate rather than
an effect of selective survival and/or proliferation. This instructive mechanism depended on the local and not the average density of the
cells. This local signal could be mimicked by membrane extract. These
findings demonstrate the importance of membrane-bound signals in
specifying lineage and provide the first evidence for a short-range regulatory mechanism in cortical stem cell differentiation.
Key words:
cortical stem cell; density; cell contact; cell-fate
determination; smooth muscle; astrocyte
Copyright © 2000 Society for Neuroscience 0270-6474/00/20103725-11$05.00/0
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