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

ABSTRACT: 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 spatio-temporal 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 during development. Under these conditions, YFs induction led to expanded neurogenesis, increased number of upper cortical neurons, and enhanced motor and social behavior of adult mice. Additionally, controlled YF induction is tolerated by principal neurons in the adult dorsal hippocampus and prevented the development of several hallmarks of Alzheimers disease, including cognitive decline and altered molecular signatures, in the 5xFAD mouse model. Overall, these results highlight the powerful impact of YFs on neurogenesis and their potential use in brain disorders.

INSTRUMENT(S): timsTOF Pro, Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Barbara Steigenberger

LAB HEAD: Daniel del Toro

PROVIDER: PXD047104 | Pride | 2025-01-14

REPOSITORIES: pride

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			Action	DRS
	20221104_EXPL6_NiKr_SA__LC12_16_Orbi4389_Sample01.raw	Raw
	20221104_EXPL6_NiKr_SA__LC12_16_Orbi4389_Sample02.raw	Raw
	20221104_EXPL6_NiKr_SA__LC12_16_Orbi4389_Sample03.raw	Raw
	20221104_EXPL6_NiKr_SA__LC12_16_Orbi4389_Sample04.raw	Raw
	20221104_EXPL6_NiKr_SA__LC12_16_Orbi4389_Sample05.raw	Raw

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Comparison of the proteome of adult neural stem/progenitor cells (NSPCs) from tdTom-Plin2 heterozygous and wildtype control mice. These data are presented in the manuscript entitled “A fluorescent perilipin 2 knock-in mouse model reveals a high abundance of lipid droplets in the developing and adult brain” by Madsen et al. 2024.

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Microglial SHIP1 controls synaptic pruning in the developing hippocampus via the complement system

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