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Pdgfragene inactivation mediates tissue remodeling in hypomyelinated cerebral cortex

ABSTRACT: Inactivation of the platelet-derived growth factor receptor-α gene in Nestin-positive cells induced not only hypomyelination, but also aberrant blood vessel formation and axonal degeneration in genetically engineered mice (N-PRα-KO mice). Here, the extended analyses, including histological study and single-cell RNA-sequencing, revealed extensive tissue remodeling in the meninges and cerebral cortex of N-PRα-KO mice. Activation of border-associated macrophages was followed by the recruitment of transcriptionally reprogrammed pial fibroblasts to new perivascular locations in the cerebral cortex. These new perivascular fibroblasts were found to be involved in self-sustaining chronic inflammation and play a critical role in tissue remodeling involving various resident cells of the meninges and cerebral cortex. Together with these facts, the heterogeneity of the fibroblasts identified here may contribute to the understanding of the pathological tissue remodeling including fibrotic process in chronic neurological diseases. Activation and mobilization of these fibroblasts may be an effective therapeutic target to prevent chronic progressive neurological diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE272031 | GEO | 2025/07/09

REPOSITORIES: GEO

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