Genome-Wide Analysis of Self-Renewal in Drosophila Neural Stem Cells by Transgenic RNAi

• Published in: Cell stem cell 2011-05, Vol.8 (5), p.580-593
• Main Authors: Neumüller, Ralph A., Richter, Constance, Fischer, Anja, Novatchkova, Maria, Neumüller, Klaus G., Knoblich, Juergen A.
• Format: Article
• Language: English
• Subjects: Alternative Splicing - genetics; Animals; Biological and medical sciences; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Differentiation - genetics; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell Survival - genetics; Cells, Cultured; Chaperonin Containing TCP-1 - genetics; Chaperonin Containing TCP-1 - metabolism; Chromatin Assembly and Disassembly - genetics; Computational Biology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila - genetics; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Genome-Wide Association Study; High Mobility Group Proteins - genetics; High Mobility Group Proteins - metabolism; Larva - genetics; Molecular and cellular biology; Multigene Family - genetics; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Resource; RNA, Messenger - analysis; Spliceosomes - genetics; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Elongation Factors - genetics; Transcriptional Elongation Factors - metabolism
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2011.02.022

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. ► Genome-wide RNAi screen finds 620 genes regulating Drosophila neural stem cells ► A set of transcriptional regulators is essential for neural stem cell self-renewal ► Brm complex, spliceosome, and TRiC/CCT-complex regulate neural differentiation ► Alternative splicing and transcriptional elongation are required in neural stem cells