Human Glial Progenitor Cells Effectively Remyelinate the Demyelinated Adult Brain

Neonatally transplanted human glial progenitor cells (hGPCs) can myelinate the brains of myelin-deficient shiverer mice, rescuing their phenotype and survival. Yet, it has been unclear whether implanted hGPCs are similarly able to remyelinate the diffusely demyelinated adult CNS. We, therefore, ask if hGPCs could remyelinate both congenitally hypomyelinated adult shiverers and normal adult mice after cuprizone demyelination. In adult shiverers, hGPCs broadly disperse and differentiate as myelinating oligodendrocytes after subcortical injection, improving both host callosal conduction and ambulation. Implanted hGPCs similarly remyelinate denuded axons after cuprizone demyelination, whether delivered before or after demyelination. RNA sequencing (RNA-seq) of hGPCs back from cuprizone-demyelinated brains reveals their transcriptional activation of oligodendrocyte differentiation programs, while distinguishing them from hGPCs not previously exposed to demyelination. These data indicate the ability of transplanted hGPCs to disperse throughout the adult CNS, to broadly myelinate regions of dysmyelination, and also to be recruited as myelinogenic oligodendrocytes later in life, upon demyelination-associated demand. [Display omitted] •Transplanted human GPCs disperse to colonize the adult mouse forebrain•Transplanted hGPCs myelinate the adult shiverer brain with functional improvement•Transplanted hGPCs similarly remyelinate cuprizone-demyelinated brain•RNA-seq of hGPCs reveals gene expression signature of human remyelination in vivo Goldman and colleagues report that transplanted human glial progenitor cells can migrate broadly within the adult brain, colonizing the host to functionally remyelinate demyelinated tissue, in both congenital and acquired models of dysmyelination. They then use RNA-seq to define how the transcriptional signatures of human GPCs change after demyelination-induced mobilization.