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.
Subject(s)
Adult Germline Stem Cells/physiology , Drosophila Proteins/metabolism , Nerve Tissue Proteins/metabolism , Adult Germline Stem Cells/metabolism , Animals , Cell Differentiation/physiology , Drosophila Proteins/genetics , 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 , Signal Transduction/physiology , Stem Cell Niche/genetics , Stem Cell Niche/physiology , Testis/metabolism , Transcription Factors/metabolismABSTRACT
Aging causes stem cell dysfunction as a result of extrinsic and intrinsic changes. Decreased function of the stem cell niche is an important contributor to this dysfunction. We use the Drosophila testis to investigate what factors maintain niche cells. The testis niche comprises quiescent "hub" cells and supports two mitotic stem cell pools: germline stem cells and somatic cyst stem cells (CySCs). We identify the cell-cycle-responsive Dp/E2f1 transcription factor as a crucial non-autonomous regulator required in CySCs to maintain hub cell quiescence. Dp/E2f1 inhibits local Activin ligands through production of the Activin antagonist Follistatin (Fs). Inactivation of Dp/E2f1 or Fs in CySCs or promoting Activin receptor signaling in hub cells causes transdifferentiation of hub cells into fully functional CySCs. This Activin-dependent communication between CySCs and hub regulates the physiological decay of the niche with age and demonstrates that hub cell quiescence results from signals from surrounding stem cells.
Subject(s)
Drosophila Proteins/metabolism , Follistatin/metabolism , Stem Cell Niche , Transcription Factors/metabolism , Activins/metabolism , Animals , Cell Proliferation , Cell Transdifferentiation , Drosophila Proteins/genetics , Drosophila melanogaster , Male , Spermatozoa/cytology , Spermatozoa/metabolism , Spermatozoa/physiology , Testis/cytology , Transcription Factors/geneticsABSTRACT
The Drosophila testis harbors two types of stem cells: germ line stem cells (GSCs) and cyst stem cells (CySCs). Both stem cell types share a physical niche called the hub, located at the apical tip of the testis. The niche produces the JAK/STAT ligand Unpaired (Upd) and BMPs to maintain CySCs and GSCs, respectively. However, GSCs also require BMPs produced by CySCs, and as such CySCs are part of the niche for GSCs. Here we describe a role for another secreted ligand, Hedgehog (Hh), produced by niche cells, in the self-renewal of CySCs. Hh signaling cell-autonomously regulates CySC number and maintenance. The Hh and JAK/STAT pathways act independently and non-redundantly in CySC self-renewal. Finally, Hh signaling does not contribute to the niche function of CySCs, as Hh-sustained CySCs are unable to maintain GSCs in the absence of Stat92E. Therefore, the extended niche function of CySCs is solely attributable to JAK/STAT pathway function.