title: Adipocyte amino acid sensing controls adult germline stem cell number via the amino acid response pathway and independently of Target of Rapamycin signaling in Drosophila.
abstract: How adipocytes contribute to the physiological control of stem cells is a critical question towards understanding the link between obesity and multiple diseases, including cancers. Previous studies have revealed that adult stem cells are influenced by whole-body physiology through multiple diet-dependent factors. For example, nutrient-dependent pathways acting within the Drosophila ovary control the number and proliferation of germline stem cells (GSCs). The potential role of nutrient sensing by adipocytes in modulating stem cells in other organs, however, remains largely unexplored. Here, we report that amino acid sensing by adult adipocytes specifically modulates the maintenance of GSCs through a Target of Rapamycin-independent mechanism. Instead, reduced amino acid levels and the consequent increase in uncoupled tRNAs trigger activation of the GCN2-dependent amino acid response pathway within adipocytes, causing increased rates of GSC loss. These studies reveal a new step in adipocyte-stem cell crosstalk.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Alissa R
authors.initials: AR
authors.lastname: Armstrong
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Laws
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA dbarbosa@jhu.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Drummond-Barbosa
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D053687:Adult Stem Cells / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism; D005260:Female; D008856:Microscopy, Fluorescence; D010053:Ovary / Q000166:cytology; D011494:Protein Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000596:Amino Acids; D029721:Drosophila Proteins; C585051:GCN2 protein, Drosophila; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases
keywords: Adipocytes; Amino acid transporters; Diet; Drosophila; Germline stem cells; Oogenesis