One of the modern challenges of cell biologists is to fully understand the mechanisms underlying cell lineage that takes place during the development of multicellular organisms. This is of importance in context of adult stem cells that alternate between quiescent and proliferation states, then dividing asymmetrically to give rise to a self-renewal stem cell plus a differentiating cell. The asymmetric determinants conferring self-renewal properties are still unknown. Of interest, in yeast Saccharomyces cerevisiae the spores that are the meiotic products of the sporulation of diploid cells display a lineage-specific asymmetric division of kinetochore components. Because the kinetochores are directly responsible for segregating chromatids during mitosis, a tempting hypothesis is that the asymmetric segregation is involved in nonrandom segregation of sister chromatids to daughter cells immediately after meiosis. The phenotype described provides an avenue through which such a nonrandom pattern of chromatid segregation could be achieved and concurrently provides a new yeast model for the cellular asymmetry to characterize determinants of the asymmetry. The power of the budding yeast S. cerevisiae in combination with various approaches, including proteomics, genetics and cell biology, will be utilized i) to identify the key properties of cell cycle control and DNA replication in the first cell cycle after exit from quiescence, ii) to characterize the full complement of epigenetic marks/proteins that segregate asymmetrically after this first division, iii) to unravel the mechanisms underlying their asymmetric distribution to daughter cells and iv) to determine which are the cell fate determinants responsible for the establishment of a cell lineage.
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