The rates of adult neurogenesis and oligodendrogenesis are linked to cell cycle regulation through p27-dependent gene repression of SOX2

• DOI: 10.1007/s00018-022-04676-6
• Publication Date: 2023-01-11T03:02:46Z
• Authors: Ana Domingo-Muelas; Jose Manuel Moran...; Verónica Moncho-Amor; Antonio Jordán-Pla; Ana Pérez-Villalba; Pau Carrillo-Barberà; Germán Belenguer; Eva Porlan; Martina Kirstein; Oriol Bachs; Sacri R. Ferrón; Robin Lovell-Badge; Isabel Fariñas
• Keywords: Neuroblast; Progenitor

Cell differentiation involves profound changes in global gene expression that often has to occur coordination with cell cycle exit. Because cyclin-dependent kinase inhibitor p27 reportedly regulates proliferation of neural progenitor cells the subependymal neurogenic niche adult mouse brain, but can also have effects on expression, we decided molecularly analyze its role neurogenesis and oligodendrogenesis. At level, show restricts residual activity after mitogen withdrawal antagonize cycling, it is not essential for By integrating genome-wide chromatin accessibility data, find coincidentally necessary repress many genes involved transit from multipotentiality differentiation, including those coding transcription factors SOX2, OLIG2 ASCL1. Our data reveal both a direct association regulatory sequences three an additional hierarchical relationship where repression Sox2 leads reduced levels downstream targets Olig2 Ascl1. In vivo, required regulation proper level SOX2 neuroblasts oligodendroglial timely exit lineage-dependent manner.