Return to quiescence of mouse neural stem cells by degradation of a proactivation protein

• Published in: Science (American Association for the Advancement of Science) Vol. 353; no. 6296; pp. 292 - 295
• Main Authors: Urbán, Noelia, van den Berg, Debbie L. C., Forget, Antoine, Andersen, Jimena, Demmers, Jeroen A. A., Hunt, Charles, Ayrault, Olivier, Guillemot, François
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 15.07.2016; The American Association for the Advancement of Science
• Subjects: Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Adult Stem Cells - physiology; Adults; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Brain; Cell Proliferation; Degradation; Hippocampus; Hippocampus - cytology; Hippocampus - embryology; Maintenance; Mice; Mice, Knockout; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neural Stem Cells - physiology; Neurogenesis; Neurons; Pools; Protein Stability; Proteins; Proteolysis; Stem cells; Transcription factors; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaf4802

Quiescence is essential for long-term maintenance of adult stem cells. Niche signals regulate the transit of stem cells from dormant to activated states. Here, we show that the E3-ubiquitin ligase Huwe1 (HECT, UBA, and WWE domain–containing 1) is required for proliferating stem cells of the adult mouse hippocampus to return to quiescence. Huwe1 destabilizes proactivation protein AscI1 (achaete-scute family bHLH transcription factor 1) in proliferating hippocampal stem cells, which prevents accumulation of cyclin Ds and promotes the return to a resting state. When stem cells fail to return to quiescence, the proliferative stem cell pool becomes depleted. Thus, long-term maintenance of hippocampal neurogenesis depends on the return of stem cells to a transient quiescent state through the rapid degradation of a key proactivation factor.