Stem Cell Select

Stem cell biology covers a wide range of topics, as exemplified by the articles in this special review issue and the papers highlighted in this Stem Cell Select. Understanding the interactions of stem cells with their surroundings—whether they be Drosophila germ cells, human bone-forming precursors, or mouse immune modulators—will reveal important target mechanisms that can be exploited therapeutically to promote homing of stem cells to the correct location and to modulate stem cell fate in situ. Developing methods to generate differentiated cells of a desired lineage from stem cells, such as muscle precursors, as well as identifying stem cell populations that give rise to unwanted populations, such as tumor cells, will also be key for moving the field of regenerative medicine forward. To translate stem cell biology into therapeutic action will necessitate that challenges be tackled from a range of angles using diverse animal model systems. Studies of Drosophila germ stem cells (GSCs) have provided an essential framework for understanding how these cells interact with their niche, a model that has been applied to other stem cells in a variety of lineages. In the Drosophila ovarium, female GSCs exhibit E-cadherin-dependent binding to the cap cells, which constitute the cellular component of their stem cell niche. Bone morphogenetic proteins (BMPs) produced by the niche inhibit expression of the differentiation-inducing genes bam and bgcn. Indeed, GSCs unable to express either of these proteins are blocked in a stem cell-like state and have been shown to accumulate beyond points of cap cell contact. In their new study, Ting Xie and colleagues (Jin et al., 2008) have used bam and bgcn mutant flies to reveal that stem cells are, in fact, capable of competing for physical contact with their niche. By clonally marking a fraction of existing GSCs and calculating the relative loss of marked GSCs over time—which is consistent with the expected turnover of GSCs during differentiation—the authors observed that marked bgcn-mutant GSCs were more often retained in the niche relative to control GSCs. More dramatically, niches became increasingly occupied with marked bam-deficient GSCs over time, indicating that wild-type GSCs can be displaced entirely. The mechanism behind the increased competitiveness of the bam and bgcn mutant GSCs appears to involve E-cadherin, as the prolonged maintenance of bgcn-mutant GSCs was overcome in compound mutant flies that also lacked E-cadherin expression. Furthermore, using either marked bam-deficient flies, or a model of heat-inducible bam overexpression, E-cadherin …