title: Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation.
abstract: Complex regulatory networks regulate stem cell behavior and contributions to tissue growth, repair, and homeostasis. A full understanding of the networks controlling stem cell self-renewal and differentiation, however, has not yet been realized. To systematically dissect these networks and identify their components, we performed an unbiased, transcriptome-wide in vivo RNAi screen in female Drosophila germline stem cells (GSCs). Based on characterized cellular defects, we classified 646 identified genes into phenotypic and functional groups and unveiled a comprehensive set of networks regulating GSC maintenance, survival, and differentiation. This analysis revealed an unexpected role for ribosomal assembly factors in controlling stem cell cytokinesis. Moreover, our data show that the transition from self-renewal to differentiation relies on enhanced ribosome biogenesis accompanied by increased protein synthesis. Collectively, these results detail the extensive genetic networks that control stem cell homeostasis and highlight the intricate regulation of protein synthesis during differentiation.
authors.affiliation: Howard Hughes Medical Institute and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Sanchez
authors.affiliation: Howard Hughes Medical Institute and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: felipe.teixeira@med.nyu.edu.
authors.forename: Felipe Karam
authors.initials: FK
authors.lastname: Teixeira
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Czech
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Preall
authors.affiliation: Howard Hughes Medical Institute and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Zamparini
authors.affiliation: Howard Hughes Medical Institute and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA; Department of Biology, Farmingdale State College, State University of New York, Farmingdale, NY 11735, USA.
authors.forename: Jessica R K
authors.initials: JR
authors.lastname: Seifert
authors.affiliation: Howard Hughes Medical Institute and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Malone
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.affiliation: Howard Hughes Medical Institute and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: ruth.lehmann@med.nyu.edu.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002466:Cell Nucleolus / Q000473:pathology; D002470:Cell Survival / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D005854:Germ Cells / Q000166:cytology*; D006984:Hypertrophy; D001678:Organelle Biogenesis; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D014176:Protein Biosynthesis; D034622:RNA Interference; D012270:Ribosomes / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*; D059467:Transcriptome / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D039561:Eukaryotic Initiation Factor-4E