96 Oral - Stem Cells, Regeneration, and Tissue Repair
Friday April 08, 10:30 AM - 10:45 AM

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


Authors:
CHEN YUAN TSENG 1; Michael Burel 1; Michael Cammer 1; Sneh Harsh 1; Maria Sol Flaherty 1; Stefan Baumgartner 2; Erika Bach 1

Affiliations:
1) NYU Grossman School of Medicine, New York, NY; 2) Department of Experimental Medical Sciences, Lund University, 22184 Lund, Sweden

Keywords:
b. germline stem cell; b. germline stem cell

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 the influence of GSC competition may extend beyond individual stem cell niche dynamics to population-level allelic drift and evolution.