Centromere proteins are asymmetrically distributed between newly divided germline stem and daughter cells and maintain a balanced niche in Drosophila males

Abstract

Stem cells can undergo asymmetric cell division (ACD) giving rise to one new stem cell and one differentiating daughter cell. 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. A model of ‘mitotic drive’ has been proposed in GSCs such that stronger and earlier centromere and kinetochore interactions with microtubules bias sister chromatid segregation. Here we show that in Drosophila males, centromere proteins CID, CAL1 and CENP-C are asymmetrically distributed in newly divided GSCs and daughter cells in S-phase. We find that CID overexpression, 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, important for maintaining tissue homeostasis. Overexpression of CAL1 does not disrupt asymmetry, but instead drives germ cell proliferation in the niche. Our results in male GSCs are comparable to female GSCs, indicating that despite differences in signaling, organisation and niche composition, effects of centromere proteins on GSC maintenance are conserved between the sexes.

Old and newly synthesized histones are asymmetrically distributed in Drosophila intestinal stem cell divisions

“…It will be intriguing to explore in the future what histone modifications are associated with old versus new histones. Furthermore, asymmetric sister centromere in recognizing sister chromatids during ACD has also been reported in Drosophila male GSCs (Ranjan et al, 2019;Kochendoerfer et al, 2021Kochendoerfer et al, , 2023) and female GSCs Dattoli et al, 2020;Carty et al, 2021;Kochendoerfer et al, 2021). Asymmetric inheritance of old versus new centromere-specific histone variant CENP-A/CID has also been reported in the Drosophila ISCs (Garcia Del Arco et al, 2018).…”