chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche

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2022
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Tseng, Chen-Yuan
Burel, Michael
Cammer, Michael
Harsh, Sneh
Flaherty, Maria Sol
Bach, Erika A.
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Developmental Cell ; 57 (2022), 1. - pp. 80-94.e7. - Cell Press. - ISSN 1534-5807. - eISSN 1878-1551
Abstract
Niches maintain a finite pool of stem cells via restricted space and short-range signals. Stem cells compete for limited niche resources, but the mechanisms regulating competition are poorly understood. Using the Drosophila testis model, we show that germline stem cells (GSCs) lacking the transcription factor Chinmo gain a competitive advantage for niche access. Surprisingly, chinmo−/− GSCs rely on a new mechanism of competition in which they secrete the extracellular matrix protein Perlecan to selectively evict non-mutant GSCs and then upregulate Perlecan-binding proteins to remain in the altered niche. Over time, the GSC pool can be entirely replaced with chinmo−/− cells. As a consequence, the mutant chinmo allele acts as a gene drive element; the majority of offspring inherit the allele despite the heterozygous genotype of the parent. Our results suggest that the influence of GSC competition may extend beyond individual stem cell niche dynamics to population-level allelic drift and evolution.
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ISO 690TSENG, Chen-Yuan, Michael BUREL, Michael CAMMER, Sneh HARSH, Maria Sol FLAHERTY, Stefan BAUMGARTNER, Erika A. BACH, 2022. chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche. In: Developmental Cell. Cell Press. 57(1), pp. 80-94.e7. ISSN 1534-5807. eISSN 1878-1551. Available under: doi: 10.1016/j.devcel.2021.12.004
BibTex
@article{Tseng2022chinm-56455,
  year={2022},
  doi={10.1016/j.devcel.2021.12.004},
  title={chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche},
  number={1},
  volume={57},
  issn={1534-5807},
  journal={Developmental Cell},
  pages={80--94.e7},
  author={Tseng, Chen-Yuan and Burel, Michael and Cammer, Michael and Harsh, Sneh and Flaherty, Maria Sol and Baumgartner, Stefan and Bach, Erika A.}
}
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