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cc-by (c) Shen, Yi Ru et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/226992

Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming

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Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs in the mouse brain in a controlled spatiotemporal manner in two different scenarios: brain development and adult stages in the context of neurodegeneration. Embryonic induction of YFs perturbed cell identity of both progenitors and neurons, but transient and low-level expression is tolerated by these cells. Under these conditions, YF induction led to progenitor expansion, an increased number of upper cortical neurons and glia, and enhanced motor and social behavior in adult mice. Additionally, controlled YF induction is tolerated by principal neurons in the adult dorsal hippocampus and prevented the development of several hallmarks of Alzheimer’s disease, including cognitive decline and altered molecular signatures, in the 5xFAD mouse model. These results highlight the powerful impact of YFs on neural proliferation and their potential use in brain disorders.

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SHEN, Yi ru, ZABALLA LARRINAGA, Sofía, BECH, Xavier, SANCHO BALSELLS, Anna, RODRIGUEZ NAVARRO, Irene, CIFUENTES DÍAZ, Carmen, SEYIT BREMER, Gönül, CHUN, Seung hee, STRAUB, Tobias, ABANTE LLENAS, Jordi, MERINO VALVERDE, Iñaki, RICHART, Laia, GUPTA, Vipul, LI, Hao yi, BALLASCH, Iván, ALCAZAR, Noelia, ALBERCH I VIÉ, Jordi, CANALS I COLL, Josep m., ABAD, María, SERRANO, Manuel, KLEIN, Rüdiger, GIRALT TORROELLA, Albert, TORO RUIZ, Daniel del. Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming. _Cell Stem Cell_. 2024. Vol. 31, núm. 12, pàgs. 1741-1759. [consulta: 26 de febrer de 2026]. ISSN: 1934-5909. [Disponible a: https://hdl.handle.net/2445/226992]

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