Localized microglia dysregulation impairs central nervous system myelination in development.

ABSTRACT: Myelination of neuronal axons is a critical aspect of central nervous system development and function. However, the fundamental cellular and molecular mechanisms influencing human developmental myelination and its failure are not fully understood. Here, we used digital spatial transcriptomics of a rare bank of human developing white matter to uncover that a localized dysregulated innate immune response is associated with impeded myelination. We identified that poorly myelinating areas have a distinct signature of Type II interferon signalling in microglia/macrophages, relative to adjacent myelinating areas. This is associated with a surprising increase in mature oligodendrocytes, which fail to form myelin processes appropriately. We functionally link these findings by showing that conditio

SUBMITTER: Holloway RK 

PROVIDER: S-EPMC10035254 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature