Abstract
Proper stem cell activity in tissues ensures the correct balance between proliferation and differentiation, thus allowing tissue homeostasis and repair. The Drosophila ovary develops well-defined niches that contain on average 2–4 germline stem cells (GSCs), whose maintenance depends on systemic signals and local factors. A known player in the decline of tissue homeostasis is ageing, which correlates with the waning of resident stem cell populations. In Drosophila, ovaries from old females contain fewer GSCs than those from young flies. We isolated niche cells of aged ovaries, performed a transcriptomic analysis and identified mastermind (mam) as a factor for Drosophila ovarian niche functionality during ageing. We show that mam is upregulated in aged niche cells and that we can induce premature GSC loss by overexpressing mam in otherwise young niche cells. High mam levels in niche cells induce reduced Hedgehog amounts, a decrease in cadherin levels and a likely increase in reactive oxygen species, three scenarios known to provoke GSC loss. Mam is a canonical co-activator of the Notch pathway in many Drosophila tissues. However, we present evidence to support a Notch-independent role for mam in the ovarian germline niche.
Highlights
Stem cells are essential for tissue homeostasis and are involved in the regeneration of damaged organs
We identified 30 upregulated and 32 downregulated genes in four-week-old females compared with one-week-old controls
Considering that mam was the only gene upregulated in the three-week-old sample and that it maintained a higher expression in older cells, we decided to analyse in deeper detail the role of mam during ovarian niche ageing
Summary
Stem cells are essential for tissue homeostasis and are involved in the regeneration of damaged organs. Ageing stem cells show changes in the expression of genes involved in the preservation of genomic integrity, and in transcriptional and epigenetic regulation; they can display both declined responsiveness to extrinsic signals and impaired adhesion to support cells or extracellular matrix; and they can increase intracellular concentrations of reactive oxygen species (ROS), accumulate DNA damage and show slower proliferation and deficient selfrenewing divisions [2,3,4,5,6,7,8]. To try to identify new genes required in niche cells and involved in GSC depletion with ageing, we embarked upon a transcriptomic analysis of maturing niche support cells in Drosophila and found a discrete number of candidate genes whose transcription was regulated with age. That mam participates in ovarian niche ageing independent of the Notch pathway
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