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bioRxiv · 10.1101/631598

CENP-A drives asymmetric cell division and maintains stem identity

Dattoli, A. A.·Carty, B. L.·Kochendoerfer, A. M.·Walshe, A. E.·Dunleavy, E. M.
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Abstract

Centromeres, chromosomal loci essential for genome integrity, are epigenetically defined by CENP-A-containing chromatin. Recent studies suggest that parental CENP-A is asymmetrically distributed upon stem cell asymmetric division. However, a direct link between centromeres and stem cell identity has not been demonstrated. We show that Drosophila female germline stem cells (GSCs) and neuroblasts assemble centromeres between G2-phase and prophase, requiring CYCLIN A. Intriguingly, chromosomes that will be inherited by GSCs incorporate more CENP-A and capture more spindle fibers at pro-metaphase. Furthermore, over-expression of CAL1 (Drosophila CENP-A assembly factor) causes GSC-like tumours, while over-expression of both CENP-A and CAL1 promotes stem cell self-renewal. Finally, once centromeres have been assembled in GSCs, continued CENP-A assembly is not required in differentiating cells outside of the niche and CAL1 becomes dispensable. According to our results CENP-A regulates stem cell identity/maintenance. Moreover, crucial centromere assembly occurs in the niche prior to oocyte meiosis.

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Dattoli, A. A., Carty, B. L., Kochendoerfer, A. M., Walshe, A. E., Dunleavy, E. M.. 2019-05-08. CENP-A drives asymmetric cell division and maintains stem identity. https://doi.org/10.1101/631598

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