title: An Aminopeptidase in the Drosophila Testicular Niche Acts in Germline Stem Cell Maintenance and Spermatogonial Dedifferentiation.
abstract: Extrinsic cues from the niche are known to regulate adult stem cell self-renewal versus differentiation. Here, we report that an aminopeptidase Slamdance (Sda) acts in the Drosophila testicular niche to maintain germline stem cells (GSCs) and regulate progenitor germ cell dedifferentiation. Mutations in sda lead to dramatic testicular niche deterioration and stem cell loss. Recombinant Sda has specific aminopeptidase activity in vitro, and the in vivo function of Sda requires an intact aminopeptidase domain. Sda is required for accumulation of mature DE-cadherin, and overexpression of DE-cadherin rescues most sda mutant phenotypes, suggesting that DE-cadherin is an important target of Sda. Finally, Sda is both necessary and sufficient to promote dedifferentiation during aging and recovery from genetically manipulated depletion of GSCs. Together, our results suggest that a niche factor promotes both stem cell maintenance and progenitor cell dedifferentiation.
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Lim
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Shiv
authors.initials: S
authors.lastname: Gandhi
authors.affiliation: Institute of Molecular Medicine and Cell Research, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Biniossek
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Molecular Medicine and Cell Research and BIOSS Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schilling
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Siniša
authors.initials: S
authors.lastname: Urban
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA. Electronic address: xchen32@jhu.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D054337:Cell Dedifferentiation; D000066673:Cell Self Renewal; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D055153:Stem Cell Niche; D013737:Testis / Q000166:cytology / Q000254:growth & development*
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C000609534:jus protein, Drosophila; C422745:suppressor of DnaA, Bacillus subtilis; D000626:Aminopeptidases