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

First Author  Shen YR Year  2024
Journal  Cell Stem Cell PubMed ID  39426381
Mgi Jnum  J:358123 Mgi Id  MGI:7779444
Doi  10.1016/j.stem.2024.09.013 Citation  Shen YR, et al. (2024) Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming. Cell Stem Cell
abstractText  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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