RT Journal Article
SR Electronic
T1 Human glial progenitor cells effectively remyelinate the demyelinated adult brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 822494
DO 10.1101/822494
A1 Martha Windrem
A1 Steven Schanz
A1 Lisa Zou
A1 Devin Chandler-Militello
A1 Nicholas J. Kuypers
A1 John N. Mariani
A1 Steven A. Goldman
YR 2019
UL http://biorxiv.org/content/early/2019/10/31/822494.abstract
AB Human glial progenitor cells (hGPCs) can completely myelinate the brains of congenitally hypomyelinated shiverer mice, rescuing the phenotype and extending or normalizing the lifespan of these mice. We asked if implanted hGPCs might be similarly able to broadly disperse and remyelinate the diffusely and/or multicentrically-demyelinated adult CNS. In particular, we asked if fetal hGPCs could effectively remyelinate both congenitally hypomyelinated adult axons, and axons acutely demyelinated in adulthood, using adult shiverer mice and cuprizone-demyelinated mice, respectively. We found that hGPCs broadly infiltrate the adult CNS after callosal injection, and robustly myelinate congenitally-unmyelinated axons in adult shiverer. Moreover, implanted hGPCs similarly remyelinated denuded axons after cuprizone demyelination, whether they were delivered prior to or after initial cuprizone demyelination. Extraction and FACS of hGPCs from cuprizone-demyelinated brains in which they had been resident, followed by RNA-seq of the isolated human hGPCs, revealed their activation of transcriptional programs indicating their initiation of oligodendrocyte differentiation and myelination. These data indicate the ability of transplanted hGPCs to disperse throughout the adult CNS, to myelinate dysmyelinated regions encountered during their parenchymal colonization, and to also be recruited as myelinating oligodendrocytes at later points in life, upon demyelination-associated demand.