Asymmetric Segregation of Damaged Cellular Components in Spatially Structured Multicellular Organisms
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Abstract:
The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage segregation, we have developed a mathematical model describing ageing mammalian tissue, that is, a multicellular system of somatic cells that do not rejuvenate at cell division. To illustrate the applicability of the model, we specifically consider damage incurred by mutations to mitochondrial DNA, which are thought to be implicated in the mammalian ageing process. We show analytically that the asymmetric distribution of damaged cellular components reduces the overall damage level and increases the longevity of the cell population. Motivated by the experimental reports of damage segregation in human embryonic stem cells, dividing symmetrically with respect to cell-fate, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a wider range of cell types than previously thought.Keywords:
Multicellular organism
Asymmetric cell division
Cell fate determination
Asymmetric cell division
Cell fate determination
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Asymmetric cell division
Cell fate determination
Cell polarity
Polarity (international relations)
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Asymmetric cell division
Cell fate determination
Polarity (international relations)
Cell polarity
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Asymmetric cell division
Multicellular organism
Cell fate determination
Cell polarity
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Cell mitoses fall into two categories: symmetric division and asymmetric division in terms of whether the cell-fate determinants are distributed to the two daughter cells equally or not.The regulations of cell division modes play a critical role in the cell proliferation and differentiation during embryogenesis.Many molecules participate in this procedure.The major function of Par complex, Crb complex and Scrib complex is to direct the asymmetric localization of cell-fate determinants such as Numb through their interaction with LgI and DIg, to establish cell polarity.However, Incuteable, Pins and G protein complex works-mainly on the control of spindle orientation.Through coordination of spindle orientation and asymmetric localization of cell-fate determinants in mitosis, they eventually lead to special mode of cell division.
Asymmetric cell division
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Cell fate determination
Cell polarity
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Cell fate determination
Asymmetric cell division
Lineage (genetic)
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Cell fate determination
Asymmetric cell division
Lineage (genetic)
Polarity (international relations)
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During development, cell division often generates two daughters with different developmental fates. Distinct daughter identities can result from the physical polarity and size asymmetry itself, as well as the subsequent activation of distinct fate programmes in each daughter. Asymmetric divisions are a feature of the C. elegans seam lineage, in which a series of post-embryonic, stem-like asymmetric divisions give rise to an anterior daughter that differentiates and a posterior daughter that continues to divide. Here we have investigated the role of non-muscle myosin II (nmy-2) in these asymmetric divisions. We show that nmy-2 does not appear to be involved in generating physical division asymmetry, but nonetheless is important for specifying differential cell fate. While cell polarity appears normal, and chromosome and furrow positioning remains unchanged when nmy-2 is inactivated, seam cell loss occurs through inappropriate terminal differentiation of posterior daughters. This reveals a role for nmy-2 in cell fate determination not obviously linked to the primary polarity determination mechanisms it has been previously associated with.
Asymmetric cell division
Cell fate determination
Polarity (international relations)
Cell polarity
Lineage (genetic)
Daughter
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Multicellular organism
Asymmetric cell division
Model Organism
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Polarity (international relations)
Asymmetric cell division
Cell polarity
Daughter
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