A novel niche-specific aminopepetidase regulates dedifferentiation of progenitor germ cells in Drosophila testis. Cindy Lim, Xin Chen. Biology, Johns Hopkins University, Baltimore, MD.

   Understanding molecular mechanism underlying stem cells maintenance and proper differentiation is the key to effectively advance stem cells therapy in medicine. To accomplish this aim, we have systematically analyzed transcription profile of normally developing germ cells at discrete but continuous differentiation stages in male Drosophila. One of our most exciting finding is a novel gene slamdance (sda) which expressed specifically in Drosophila testis niche. The sda gene encodes an aminopeptidase, an enzyme whose function has not been previously shown in any stem cell system. We found that loss-of-function in sda leads to dramatic abnormalities in the testis niche, including deterioration of the niche architecture and loss of stem cells. We determined that loss of germline stem cells (GSCs) in the sda mutant is caused by defects in both dedifferentiation of progenitor cells and cadherin-dependent maintenance of GSCs. The molecular mechanism governing progenitor cell dedifferentiation pathway is mostly unknown. We showed that Sda is the first niche specific factor that affect dedifferentiation pathway. Further studies using loss-of-function and gain-of-function assays showed that that Sda is both necessary and sufficient to promote dedifferentiation of progenitor germ cells through the requirement of its catalytic domain. Therefore, our findings provide in vivo evidence that a novel niche-specific aminopeptidase promotes dedifferentiation to repopulate the stem cell niche under both physiological conditions and genetically manipulated depletion of stem cells. Our results advance understanding how a niche-specific peptidase influences differentiation versus dedifferentiation decision of progenitor cells in an endogenous stem cell system.