Asymmetry of stem cell fate and the potential impact of the niche |
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Authors: | Ingo Roeder Ronny Lorenz |
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Institution: | (1) IMISE, University of Leipzig, Haertelstr. 16-18, D-04017 Leipzig, Germany |
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Abstract: | Asymmetric cell division is a common concept to explain the capability of stem cells to simultaneously produce a continuous
output of differentiated cells and to maintain their own population of undifferentiated cells. Whereas for some stem cell
systems, an asymmetry in the division process has explicitly been demonstrated, no evidence for such a functional asymmetry
has been shown for hematopoietic stem cells (HSC) so far. This raises the question regarding whether asymmetry of cell division
is a prerequisite to explain obvious heterogeneity in the cellular fate of HSC.
Through the application of a mathematical model based on self-organizing principles, we demonstrate that the assumption of
asymmetric stem cell division is not necessary to provide a consistent account for experimentally observed asymmetries in
the development of HSC. Our simulation results show that asymmetric cell fate can alternatively be explained by a reversible
expression of functional stem cell potentials, controlled by changing cell-cell and cell-microenvironment interactions. The
proposed view on stem cell organization is pointing to the potential role of stem cell niches as specific signaling environments,
which induce developmental asymmetries and therefore, generate cell fate heterogeneity.
The self-organizing concept is fully consistent with the functional definition of tissue stem cells. It naturally includes
plasticity phenomena without contradicting a hierarchical appearance of the stem cell population. The concept implies that
stem cell fate is only predictable in a probabilistic sense and that retrospective categorization of stem cell potential,
based on individual cellular fates, provides an incomplete picture. |
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Keywords: | Stem cell fate niche asymmetric division mathematical model simulation analysis |
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