One Sentence Summary
During Drosophila male germline stem cell division, asymmetric sister centromeres communicate with spindle microtubule differentially and bias sister chromatid segregation.
SUMMARY Through mitosis, one mother cell gives rise to two identical daughter cells. The mitotic spindle interacts with sister chromatids to ensure their equal partitioning. By inheriting the identical genetic information, a crucial question is how cells become different to fulfill distinct functions during development and homeostasis. The “strand-specific imprinting and selective chromatid segregation” and “silent sister chromatid” hypotheses propose that epigenetic differences at the sister centromeres contribute to biased sister chromatid attachment and segregation during mitosis. However, direct in vivo evidence has never been shown. Here we report that a stem cell-specific ‘mitotic drive’ ensures biased sister chromatid attachment and asymmetric epigenetic inheritance. We found that temporally asymmetric microtubule activities direct polarized nuclear envelope breakdown, allowing for the preferential recognition and attachment of sister centromeres with quantitative differences. This communication occurs in a spatiotemporally regulated manner to ensure selective attachment of sister chromatids by the mitotic machinery. Abolishment of the microtubule asymmetries result in randomized sister chromatid segregation. Our results demonstrate that the cis-asymmetry at chromatids tightly coincide and coordinate with the trans-asymmetry from the mitotic machinery, to allow for differential attachment and segregation of genetically identical but epigenetically distinct sister chromatids. Together these results provide the first direct in vivo evidence to support the above hypotheses in asymmetrically dividing stem cells. We anticipate that this ‘mitotic drive’ mechanism could be widely used in other developmental context to achieve distinct cell fates between the two genetically identical daughter cells.