The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein


Neurogenesis in the developing human cerebral cortex occurs at a particularly slow rate owing in part to cortical neural progenitors preserving their progenitor state for a relatively long time, while generating neurons. How this balance between the progenitor and neurogenic state is regulated, and whether it contributes to species-specific brain temporal patterning, is poorly understood. Here, we show that the characteristic potential of human neural progenitor cells (NPCs) to remain in a progenitor state as they generate neurons for a prolonged amount of time requires the amyloid precursor protein (APP). In contrast, APP is dispensable in mouse NPCs, which undergo neurogenesis at a much faster rate. Mechanistically, APP cell-autonomously contributes to protracted neurogenesis through suppression of the proneurogenic activator protein-1 transcription factor and facilitation of canonical WNT signaling. We propose that the fine balance between self-renewal and differentiation is homeostatically regulated by APP, which may contribute to human-specific temporal patterns of neurogenesis.

Authors Shabani K, Pigeon J, Benaissa Touil Zariouh M, Liu T, Saffarian A, Komatsu J, Liu E, Danda N, Becmeur-Lefebvre M, Limame R, Bohl D, Parras C, Hassan BA
Journal Science advances
Publication Date 2023 Jun 16;9(24):eadd5002
PubMed 37327344
PubMed Central PMC10275593
DOI 10.1126/sciadv.add5002

Research Projects

Cell Lines