Abstract
Neutral competition, an emerging feature of stem cell homeostasis, posits that individual stem cells can be lost and replaced by their neighbors stochastically, resulting in chance dominance of a clone at the niche. A single stem cell with an oncogenic mutation could bias this process and clonally spread the mutation throughout the stem cell pool. The Drosophila testis provides an ideal system for testing this model. The niche supports two stem cell populations that compete for niche occupancy. Here, we show that cyst stem cells (CySCs) conform to the paradigm of neutral competition and that clonal deregulation of either the Hedgehog (Hh) or Hippo (Hpo) pathway allows a single CySC to colonize the niche. We find that the driving force behind such behavior is accelerated proliferation. Our results demonstrate that a single stem cell colonizes its niche through oncogenic mutation by co-opting an underlying homeostatic process.
Highlights
The ability of a stem cell to continually generate offspring for tissue maintenance depends on its ability to remain and renew at the niche
In this study we characterized the behavior of somatic cyst stem cells (CySCs) in the Drosophila testis and explored the molecular mechanisms that regulate their ability to compete with their neighbors for limited space at the niche
We found that single stem cell clones bias stem cell replacement dynamics in their favor, leading to non-neutral competition, when they had increases in Hh signaling, Yki activity or in the rate of proliferation, but not when JAK/STAT signaling or adhesion were dys-regulated
Summary
The ability of a stem cell to continually generate offspring for tissue maintenance depends on its ability to remain and renew at the niche. Recent work has revealed that the latter, termed neutral competition, is an emerging feature of stem cell homeostasis This model states that individual stem cells can be stochastically lost and replaced by their neighbors, resulting in chance dominance of a clone at the niche. The fact that loss and gain of stem cells occurs opens the possibility of a transformed stem cell exploiting this process in its favor and achieving clonal dominance Such behavior theoretically could underlie the observation of tumor-initiating cells in certain types of cancer (Reya et al, 2001) and has recently been reported for mouse intestinal stem cells (Vermeulen et al, 2013; Snippert et al, 2014)
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