Persistent competition among stem cells and their daughters in theDrosophilaovary germline niche

Abstract

Cell competition is a short-range cell-cell interaction leading to the proliferation of winner cells at the expense of losers, although either cell type shows normal growth in homotypic environments. Drosophila Myc (dMyc; Dm -FlyBase) is a potent inducer of cell competition in wing epithelia, but its role in the ovary germline stem cell niche is unknown. Here, we show that germline stem cells (GSCs) with relative lower levels of dMyc are replaced by GSCs with higher levels of dMyc. By contrast, dMyc-overexpressing GSCs outcompete wild-type stem cells without affecting total stem cell numbers. We also provide evidence for a naturally occurring cell competition border formed by high dMyc-expressing stem cells and low dMyc-expressing progeny, which may facilitate the concentration of the niche-provided self-renewal factor BMP/Dpp in metabolically active high dMyc stem cells. Genetic manipulations that impose uniform dMyc levels across the germline produce an extended Dpp signaling domain and cause uncoordinated differentiation events. We propose that dMyc-induced competition plays a dual role in regulating optimal stem cell pools and sharp differentiation boundaries, but is potentially harmful in the case of emerging dmyc duplications that facilitate niche occupancy by pre-cancerous stem cells. Moreover, competitive interactions among stem cells may be relevant for the successful application of stem cell therapies in humans.

Hh signalling is essential for somatic stem cell maintenance in the Drosophila testis niche

“…We therefore propose that competition between the somatic stem cells (Rhiner et al, 2009) is largely, although not exclusively, responsible for the loss of homozygous mutant smo CySCs and the proliferative advantage of individual ptc mutant CySCs in an otherwise heterozygous testis.…”

Cell competition: how to eliminate your neighbours

“…In this way, stem cell competition leads to the same outcome as cell competition, in that the tissue is eventually clonal. It is notable that several types of stem cells in Drosophila also compete for niche space (Zhang and Kalderon, 2001;Nystul and Spradling, 2007;Jin et al, 2008;Issigonis et al, 2009;Rhiner et al, 2009).…”

The stem cell niche: lessons from theDrosophilatestis

“…In the Drosophila ovary, in which two to three GSCs are anchored to the niche via E-cadherin-based adhesion, different levels of E-cadherin can induce competition between neighboring GSCs; GSCs that express more E-cadherin displace neighboring GSCs that express less E-cadherin . bam mutant GSCs, which express higher than normal levels of E-cadherin, are also able to displace neighboring wild-type GSCs , as are GSCs with higher levels of Dpp signaling, which promotes GSC self-renewal (Rhiner et al, 2009). Competition between neighboring GSCs might also occur in the testis, but this has not yet been reported.…”