Modeling Stem Cell Asymmetry in Yeast

For adult stem cells to both self-renew and give rise to differentiating progenitors, they must undergo an inherently asymmetric division. This defining model of asymmetric cell division requires either that stem cells preferentially distribute internal factors, thereby maintaining a stem cell phenotype in one lineage, or that extrinsic signals determine the fate of daughter cells, allowing the maintenance of one stem cell lineage. Although microbial systems are often used to model asymmetry, lineage-specific asymmetry has not been characterized in these organisms. Recently, we identified a stem-cell-like lineage-specific pattern of kinetochore asymmetry in postmeiotic yeast spores. Because the function of the kinetochore is to segregate chromosomes, this asymmetry has the potential to segregate sister chromatids nonrandomly. This may be relevant to stem cells because more than 30 years ago, it was proposed that stem cells selectively segregate one strand of their chromosomes into the self-renewing stem cell lineage (Cairns 1975). Although advanced labeling methods have provided evidence to both support and refute this hypothesis, it remains unclear how nonrandom sister-chromatid segregation might be achieved in a stem cell lineage. We have identified a kinetochore-specific mechanism in yeast that could support lineage-specific nonrandom sister-chromatid segregation and we discuss the implications of this observation.