Author:
Ranjan Rajesh,Snedeker Jonathan,Chen Xin
Abstract
SUMMARYThrough the process of symmetric cell division, one mother cell gives rise to two identical daughter cells. Many stem cells utilize asymmetric cell division (ACD) to produce a self-renewed stem cell and a differentiating daughter cell. Since both daughter cells inherit the identical genetic information during ACD, a crucial question concerns how non-genic factors could be inherited differentially to establish distinct cell fates. It has been hypothesized that epigenetic differences at sister centromeres could contribute to biased sister chromatid attachment and segregation. 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 segregation. We have found during stem cell ACD, sister centromeres become asymmetrically enriched with proteins involved in centromere specification and kinetochore function. Furthermore, we show that that temporally asymmetric microtubule activities direct polarized nuclear envelope breakdown, allowing for the preferential recognition and attachment of microtubules to asymmetric sister kinetochores and sister centromeres. This communication occurs in a spatiotemporally regulated manner. Abolishment of either the establishment of asymmetric sister centromeres or the asymmetric microtubule emanation results in randomized sister chromatid segregation, which leads to stem cell loss. Our results demonstrate that the cis-asymmetry at sister centromeres tightly coordinates with the trans-asymmetry from the mitotic machinery to allow for differential attachment and segregation of genetically identical yet epigenetically distinct sister chromatids. Together, these results provide the first direct in vivo mechanisms for partitioning epigenetically distinct sister chromatids in asymmetrically dividing stem cells, which opens a new direction to study how this mechanism could be used in other developmental contexts to achieve distinct cell fates through mitosis.One Sentence SummaryDuring Drosophila male germline stem cell asymmetric division, sister centromeres communicate with spindle microtubules for differential attachment and segregation of sister chromatids.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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