Journal
DEVELOPMENTAL CELL
Volume 57, Issue 1, Pages 80-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2021.12.004
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Funding
- Laura and Isaac Perlmutter Cancer Center support grant NIH/NCI [P30CA016087]
- Office of the Director of the NIH [P40OD018537]
- National Human Genome Research Institute at NIH [U41 HG000739]
- NIH [R03-HD090422, R01-GM085075]
- New York State Department of Health/NYSTEM institutional training grant [C322560GG]
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This study reveals that germline stem cells lacking the transcription factor Chinmo have a competitive advantage and can replace the entire germline stem cell pool over time. The study also suggests that the influence of germline stem cell competition may extend beyond individual stem cell niche dynamics to population-level allelic drift and evolution.
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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