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

Dev Cell. 2022 Jan 10;57(1):80-94.e7. doi: 10.1016/j.devcel.2021.12.004. Epub 2021 Dec 22.

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.

Keywords: Drosophila; Dystroglycan; Perlecan; aging; biased inheritance; chinmo; competition; germline stem cell; niche; testis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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

Substances

  • Chinmo protein, Drosophila
  • Drosophila Proteins
  • Heparan Sulfate Proteoglycans
  • Nerve Tissue Proteins
  • Transcription Factors
  • perlecan