The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein.
Khadijeh ShabaniJulien PigeonMarwan Benaissa Touil ZariouhTengyuan LiuAzadeh SaffarianJun KomatsuElise LiuNatasha DandaMathilde Becmeur-LefebvreRidha LimameDelphine BohlCarlos ParrasBassem A HassanPublished in: Science advances (2023)
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.
Keyphrases
- endothelial cells
- neural stem cells
- transcription factor
- induced pluripotent stem cells
- pluripotent stem cells
- cerebral ischemia
- mesenchymal stem cells
- amino acid
- spinal cord injury
- immune response
- bone marrow
- protein protein
- small molecule
- multiple sclerosis
- magnetic resonance imaging
- inflammatory response
- toll like receptor
- genetic diversity
- risk assessment