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Hedgehog signal pathway affecting myelin development and repair through cholesterol Deregulation

GSE261881 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/10/01 Platform GPL24247
Summary
we used the active point mutant model RosaM2 to inject tamoxifen at specific postnatal time periods to induce Smo overexpression in brain OPCs. Meanwhile, we used lpc-induced acute demyelination as a pathological model to explore the effect of Smo on OL differentiation under pathological conditions. The cortex and CC of SmoM2-OE (RosaM2; pdgfra-creER) and littermates were then analyzed using rna-sequencing to explore the molecular mechanisms. Our results reveal that activing hedgehog signaling in opcs (1) affects ol proper differentiation and reduces myelination; and (2) alters cholesterol biosynthesis and trafficking in mouse oligodendrocytes. We have refined the regulatory network of oligodendrocyte development and myelination, established the functional link between the Hh signaling pathway, cholesterol homeostasis and myelination, and provided guidance for the application of Hh agonists/antagonists in the treatment of demyelination-related neurodegenerative diseases.
Published in
Hyperactivation of Hedgehog signaling impedes myelin development and repair via cholesterol dysregulation in oligodendrocytes
Fang M, Wang X, Chen L et al. · iScience 2024 · PMID 39635117 · doi:10.1016/j.isci.2024.111016
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Also filed as BioProject PRJNA1089489 and SRA study SRP496346. Searching any of these in the dataset finder brings you back here.

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