| First Author | Shabani K | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 24 | Pages | eadd5002 |
| PubMed ID | 37327344 | Mgi Jnum | J:336924 |
| Mgi Id | MGI:7492919 | Doi | 10.1126/sciadv.add5002 |
| Citation | Shabani K, et al. (2023) The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein. Sci Adv 9(24):eadd5002 |
| abstractText | 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. |
