Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation

Cell Stem Cell. 2016 Feb 4;18(2):276-90. doi: 10.1016/j.stem.2015.11.004. Epub 2015 Dec 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Nucleolus / pathology
  • Cell Survival / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Eukaryotic Initiation Factor-4E / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Genes, Insect
  • Germ Cells / cytology*
  • Hypertrophy
  • Organelle Biogenesis*
  • Peptide Chain Initiation, Translational / genetics
  • Phenotype
  • Protein Binding
  • Protein Biosynthesis*
  • RNA Interference
  • Ribosomes / metabolism*
  • Stem Cells / cytology*
  • Transcriptome / genetics


  • Drosophila Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Eukaryotic Initiation Factor-4E