Abstract
Epithelial stem cells are routinely lost or damaged during adult life and must therefore be replaced to maintain homeostasis. Recent studies indicate that stem cell replacement occurs through neutral competition in many types of epithelial tissues, but little is known about the factors that determine competitive outcome. The epithelial follicle stem cells (FSCs) in the Drosophila ovary are regularly lost and replaced during normal homeostasis, and we show that FSC replacement conforms to a model of neutral competition. In addition, we found that FSCs mutant for the basolateral junction genes, lethal giant larvae (lgl) or discs large (dlg), undergo a biased competition for niche occupancy characterized by increased invasion of neighboring FSCs and reduced loss. Interestingly, FSCs mutant for a third basolateral junction gene, scribble (scrib), do not exhibit biased competition, suggesting that Lgl and Dlg regulate niche competition through a Scrib-independent process. Lastly, we found that FSCs have a unique cell polarity characterized by broadly distributed adherens junctions and the lack of a mature apical domain. Collectively, these observations indicate that Lgl and Dlg promote the differentiation of FSC progeny to a state in which they are less prone to invade the neighboring niche. In addition, we demonstrate that the neutral drift model can be adapted to quantify non-neutral behavior of mutant clones.
Highlights
Adult stem cells are maintained within specialized microenvironments, or niches, that promote stem cell self-renewal while allowing non-stem cells to exit the niche and differentiate [1,2]
We found that the frequency of GFP- follicle stem cells (FSCs) was similar at all three time wildtype ovarioles stained for FasIII to label follicle cells, GFP to mark FSC clones, and DAPI
We have demonstrated that FSCs normally undergo neutral competition through stochastic replacement events, and that lgl- and dlg- FSCs undergo non-neutral hypercompetition with wildtype FSCs
Summary
Adult stem cells are maintained within specialized microenvironments, or niches, that promote stem cell self-renewal while allowing non-stem cells to exit the niche and differentiate [1,2] This system ensures that both the stem cell and the differentiated cell populations are replenished during normal homeostasis. Wildtype stem cell replacement is stochastic, neutral, and can be very frequent, suggesting that it is a normal part of homeostasis that reflects a robust design of tissue stem cell systems Both this process and the genetic basis for it have been studied extensively in Drosophila, and, more recently, it has become clear that stem cells regularly turn over in mammalian epithelia. The ratio of symmetric to asymmetric outcomes varies between tissue types, but in each tissue, the frequencies of symmetric division and stem cell loss must be equal in order to maintain a constant number of stem cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
