A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

Abstract

Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that,inhGPC-xenografted mice, the human donor cells continue to expand throughout theforebrain, systematically replacing the hostmurine glia. The differentiationofthe donor cellsisinfluencedbythe host environment,such that more donor cellsdifferentiated as oligodendrocytes inthe hypomyelinatedshivererbrain than in myelin wild-types, in which hGPCs were more likely to remainas progen-itors.Yetineachrecipient,both thenumberandrelativeproportionofmouseGPCsfellasafunctionoftime,concomitant withthemitotic expansion and spreadofdonor hGPCs.By ayear after neonatal xenograft, the forebrain GPC populations ofimplanted mice were largely, and often entirely, of human origin. Thus, neonatally implanted hGPCs outcompeted and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo.