Research Highlights

Nature Reports Stem Cells
Published online: 24 January 2008 | doi:10.1038/stemcells.2008.24

The space race

Simone Alves¹

Defective stem cells physically compete for space in the niche of the Drosophila ovary

How competitive is a stem cell? A recent study published in Cell Stem Cell shows that mutant germline stem cells (GSCs) can outcompete wild-type GSCs in the Drosophila ovary. Ting Xie and his team at the Stowers Institute for Medical Research, in Kansas City, Missouri, examined these tiny structures and discovered that stem cells defective in differentiation genes can physically push wild-type GSCs out of the niche.

The Drosophila ovary contains two or three GSCs, and when they divide, the differentiated cells (called cystoblasts) move away from the niche. The differentiation-promoting proteins bag of marbles (bam) and benign gonial cell neoplasm (bgcn) are expressed at high levels in cystoblasts but only at very low levels in GSCs. Lead author Zhigang Jin and colleagues mutated these genes in some GSCs so that there was no functional bam or bgcn protein. The technique they used allowed both wild-type and mutant stem cells to be present in the same niche and allowed the researchers to tell which type was which. Over time, wild-type GSCs were displaced by mutants in the ovary.

In other Drosophila systems, fast-growing cells can eliminate slow-growing cells by inducing apoptosis; however, this was not the case in the ovary, nor was the displacement a result of differentiation. "Defective GSCs don't kill other stem cells but push them out of the niche physically," Xie reveals.

To determine how this could occur, the group began looking at E-cadherin, an adhesion molecule required to anchor GSCs in the niche. Using a new 3D reconstruction technique to examine bam/bgcn and shotgun (which encodes E-cadherin) double-mutant stem cells, the group realised that GSCs defective in bam/bgcn actually accumulated more E-cadherin and had a larger surface area in contact with the niche cells than did wild-type cells in the same niche. Moreover, they discovered that expression of bam/bgcn downregulates E-cadherin in wild-type cells. This provides a neat explanation of how stem cells move away from the niche when they begin to differentiate: they express bam/bgcn at higher levels, thereby reducing the level of E-cadherin and thus diminishing their anchorage to the niche. The system also makes sense functionally, explains Xie: "You don't want differentiated cells to take up precious space in the niche." Removal of differentiating cells from the niche means that only functional stem cells remain.

Cells harbouring defective bam/bgcn proliferated at a greater rate than wild-type cells, which might also contribute to their advantage. Surprisingly, neither bone morphogenic proteins (BMP) nor the Myc oncoprotein are involved in GSC competition, despite being implicated in similar phenomena elsewhere in Drosophila development.

This work does have clinical implications for humans — understanding how E-cadherin is modulated in Drosophila could shed light on how cancer stem cells metastasize in humans, and there is already academic interest and excitement at this possibility. The authors plan to investigate which other mutations might be able to outcompete wild-type GSCs.

Author affiliation

1. Simone Alves is an intern for Nature Publishing Group in London.