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Hedgehog signal pathway affecting myelin development and repair through cholesterol Deregulation

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE261881 | GEO | 2024/10/01

REPOSITORIES: GEO

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Developmental trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell RNA sequencing

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*Possible corruption in count data files-update in progress* Disease-specific oligodendrocyte lineage cells express immunoprotective and adaptive immunity genes in multiple sclerosis

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