title: Genome-wide analysis of self-renewal in Drosophila neural stem cells by transgenic RNAi.
abstract: The balance between stem cell self-renewal and differentiation is precisely controlled to ensure tissue homeostasis and prevent tumorigenesis. Here we use genome-wide transgenic RNAi to identify 620 genes potentially involved in controlling this balance in Drosophila neuroblasts. We quantify all phenotypes and derive measurements for proliferation, lineage, cell size, and cell shape. We identify a set of transcriptional regulators essential for self-renewal and use hierarchical clustering and integration with interaction data to create functional networks for the control of neuroblast self-renewal and differentiation. Our data identify key roles for the chromatin remodeling Brm complex, the spliceosome, and the TRiC/CCT-complex and show that the alternatively spliced transcription factor Lola and the transcriptional elongation factors Ssrp and Barc control self-renewal in neuroblast lineages. As our data are strongly enriched for genes highly expressed in murine neural stem cells, they are likely to provide valuable insights into mammalian stem cell biology as well.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Neumüller
authors.forename: Constance
authors.initials: C
authors.lastname: Richter
authors.forename: Anja
authors.initials: A
authors.lastname: Fischer
authors.forename: Maria
authors.initials: M
authors.lastname: Novatchkova
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Neumüller
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D055106:Genome-Wide Association Study; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D017381:Spliceosomes / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C561453:Barc protein, Drosophila; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; C489543:SSRP protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C086469:brm protein, Drosophila; C121765:lola protein, Drosophila; D056404:Chaperonin Containing TCP-1