title: Somatic stem cell differentiation is regulated by PI3K/Tor signaling in response to local cues.
abstract: Stem cells reside in niches that provide signals to maintain self-renewal, and differentiation is viewed as a passive process that depends on loss of access to these signals. Here, we demonstrate that the differentiation of somatic cyst stem cells (CySCs) in the Drosophila testis is actively promoted by PI3K/Tor signaling, as CySCs lacking PI3K/Tor activity cannot differentiate properly. We find that an insulin peptide produced by somatic cells immediately outside of the stem cell niche acts locally to promote somatic differentiation through Insulin-like receptor (InR) activation. These results indicate that there is a local 'differentiation' niche that upregulates PI3K/Tor signaling in the early daughters of CySCs. Finally, we demonstrate that CySCs secrete the Dilp-binding protein ImpL2, the Drosophila homolog of IGFBP7, into the stem cell niche, which blocks InR activation in CySCs. Thus, we show that somatic cell differentiation is controlled by PI3K/Tor signaling downstream of InR and that the local production of positive and negative InR signals regulates the differentiation niche. These results support a model in which leaving the stem cell niche and initiating differentiation are actively induced by signaling.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 550 1st Avenue, New York, NY 10016, USA marc.amoyel@bristol.ac.uk erika.bach@nyu.edu.|Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, 550 1st Avenue, New York, NY 10016, USA.
authors.forename: Marc
authors.identifier: 0000-0002-2691-2097
authors.initials: M
authors.lastname: Amoyel
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 550 1st Avenue, New York, NY 10016, USA.
authors.forename: Kenzo-Hugo
authors.initials: KH
authors.lastname: Hillion
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 550 1st Avenue, New York, NY 10016, USA.
authors.forename: Shally R
authors.initials: SR
authors.lastname: Margolis
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 550 1st Avenue, New York, NY 10016, USA marc.amoyel@bristol.ac.uk erika.bach@nyu.edu.|Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, 550 1st Avenue, New York, NY 10016, USA.
authors.forename: Erika A
authors.identifier: 0000-0002-5997-4489
authors.initials: EA
authors.lastname: Bach
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000196:embryology*
chemical_list: D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C416303:target of rapamycin protein, Drosophila; C494917:Akt1 protein, Drosophila
keywords: Drosophila; Insulin; PI3K; Stem cell differentiation; Testis; Tor