RRC ID 70810
Author Tseng CY, Burel M, Cammer M, Harsh S, Flaherty MS, Baumgartner S, Bach EA.
Title chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche.
Journal Dev Cell
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.
Volume 57(1)
Pages 80-94.e7
Published 2022-1-10
DOI 10.1016/j.devcel.2021.12.004
PII S1534-5807(21)00993-X
PMID 34942115
PMC PMC8752517
MeSH Adult Germline Stem Cells / metabolism Adult Germline Stem Cells / physiology* Animals Cell Differentiation / physiology Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism Extracellular Matrix / metabolism Gene Expression / genetics Gene Expression Regulation, Developmental / genetics Germ Cells / metabolism Heparan Sulfate Proteoglycans / metabolism Male Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Signal Transduction / physiology Stem Cell Niche / genetics Stem Cell Niche / physiology Testis / metabolism Transcription Factors / metabolism
IF 10.092
Drosophila DGRC#111100 DGRC#104055