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bioRxiv · 10.1101/2022.09.29.510087

Asymmetric distribution of centromere proteins between germline stem and daughter cells maintains a balanced niche in Drosophila males.

Kochendoerfer, A. M.·Dunleavy, E. M.
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Abstract

In the germline, stem cells undergo asymmetric cell division (ACD) to give rise to one new stem cell as well as one daughter cell that differentiates and eventually gives rise to the gamete (egg or sperm). The silent sister hypothesis proposes the selective inheritance of one set of sister chromatids carrying specific epigenetic marks to explain how genetically identical stem and daughter cells can adopt different fates. It also proposes that centromeres of sister chromatids might differ epigenetically. In Drosophila germline stem cells (GSCs), the centromeric histone CENP-A - CID in flies - is asymmetrically distributed between sister chromatids such that chromosomes that end up in the GSC harbour more CID at centromeres. In this system, a model of mitotic drive has been proposed. According to this model, stronger and earlier centromere and kinetochore interactions with microtubules bias sister chromatid segregation during ACD. Here we show that in Drosophila males, CID, CENP-C and CAL1 are asymmetrically distributed between newly divided GSCs and daughter cells that have entered S-phase of the next cell cycle. We find that overexpression of CID, overexpression of CID together with CAL1 or CENP-C depletion disrupts CID asymmetry, with an increased pool of GSCs relative to daughter cells detectable in the niche. This result suggests a shift toward GSC self-renewal rather than differentiation, which is important to maintain tissue homeostasis. Over-expression of CAL1 does not disrupt asymmetry, nor does it affect the GSC and daughter cell balance, but instead drives germ cell proliferation in the niche. Our results in male GSCs are closely aligned with previous observations in female GSCs, indicating that despite differences in signaling, organisation and niche composition, centromere asymmetry and its effects on GSC maintenance are conserved between the sexes.

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Kochendoerfer, A. M., Dunleavy, E. M.. 2022-09-30. Asymmetric distribution of centromere proteins between germline stem and daughter cells maintains a balanced niche in Drosophila males.. https://doi.org/10.1101/2022.09.29.510087

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