Asymmetric Chromosome Establishment and Segregation During Germline Stem Cell Division

In metazoans, gametogenesis produces the only cell type capable of transmitting both genetic and epigenetic information to offspring. This process represents one of the most extensive cellular differentiation programs, often originating from germline stem cells (GSCs), as in the female and male Drosophila and C. elegans gonads. These well-defined, unipotent germline lineages provide powerful in vivo models to study epigenetic regulation in multicellular organisms. During gametogenesis, epigenetic mechanisms balance cell differentiation and cellular plasticity. This review summarizes recent findings on how asymmetric sister chromatids are established and segregated during GSC division, the initial step of gametogenesis essential for reproduction in Drosophila and C. elegans. We focus on histones, a major carrier of epigenetic information, and discuss how their inheritance is regulated during GSC asymmetric divisions. Canonical histones and histone variants are dynamically incorporated into chromatin in a cell cycle- and genomic locus-specific manner, and these chromosome-bound epigenetic differences must coordinate with the mitotic machinery to ensure their proper partitioning. Finally, we speculate how these mechanisms may extend beyond the germline, assessing their conservation across species. Understanding these processes provides critical insights into how misregulation contributes to disease and how targeted manipulation could promote tissue homeostasis and regeneration.