Abstract
BackgroundAdult stem cells are critical for tissue homeostasis; therefore, the mechanisms utilized to maintain an adequate stem cell pool are important for the survival of an individual. In Drosophila, one mechanism utilized to replace lost germline stem cells (GSCs) is dedifferentiation of early progenitor cells. However, the average number of male GSCs decreases with age, suggesting that stem cell replacement may become compromised in older flies.Methodology/Principal FindingsUsing a temperature sensitive allelic combination of Stat92E to control dedifferentiation, we found that germline dedifferentiation is remarkably efficient in older males; somatic cells are also effectively replaced. Surprisingly, although the number of somatic cyst cells also declines with age, the proliferation rate of early somatic cells, including cyst stem cells (CySCs) increases.ConclusionsThese data indicate that defects in spermatogonial dedifferentiation are not likely to contribute significantly to an aging-related decline in GSCs. In addition, our findings highlight differences in the ways GSCs and CySCs age. Strategies to initiate or enhance the ability of endogenous, differentiating progenitor cells to replace lost stem cells could provide a powerful and novel strategy for maintaining tissue homeostasis and an alternative to tissue replacement therapy in older individuals.
Highlights
In regenerative tissues, such as skin and blood, adult stem cells support tissue homeostasis by replenishing cells lost due to normal cellular turnover and/or damage throughout life
These data indicate that defects in spermatogonial dedifferentiation are not likely to contribute significantly to an aging-related decline in germline stem cells (GSCs)
Flies were moved to the restrictive temperature (29uC) for two days, which leads to a decrease in detectable Stat92E protein in germ cells and a loss of GSCs due to differentiation (Figures 1, 2)
Summary
In regenerative tissues, such as skin and blood, adult stem cells support tissue homeostasis by replenishing cells lost due to normal cellular turnover and/or damage throughout life. Stem cells are found in unique locations within a tissue, known as stem cell niches, which support stem cell self-renewal, maintenance, and survival. Stem cell self-renewal provides a means to maintain a pool of active stem cells; in some tissues, the number and/or activity of stem cells declines during aging, suggesting that changes in stem cell behavior likely contribute to reduced tissue homeostasis in older individuals (reviewed in [1]). In the Drosophila testis, male germline stem cells (GSCs) and cyst stem cells (CySCs) are located at the apical tip where they are in contact with a cluster of somatic cells called the hub (Figure 1A). Adult stem cells are critical for tissue homeostasis; the mechanisms utilized to maintain an adequate stem cell pool are important for the survival of an individual. The average number of male GSCs decreases with age, suggesting that stem cell replacement may become compromised in older flies
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