Journal
FASEB JOURNAL
Volume 20, Issue 12, Pages 2081-2092Publisher
WILEY
DOI: 10.1096/fj.05-5593com
Keywords
glial cell; bone marrow; stem cells; cell transfer
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Recent evidence indicates that microglial cells may not derive from blood circulating mature monocytes as they express features of myeloid progenitors. Here, we observed that a subpopulation of microglial cells expressed CD34 and B220 antigens during brain development. We thus hypothesized that microglia, or a subset of microglial cells, originate from blood circulating CD34(+)/B220(+) myeloid progenitors, which could target the brain under developmental or neuroinflammatory conditions. Using experimental allergic encephalomyelitis (EAE) as a model of chronic neuroinflammation, we found that a discrete population of CD34(+)/B220(+) cells expands in both blood and brain of diseased animals. In EAE mice, intravenous transfer experiments showed that macrophage-colony stimulating factor (M-CSF)-expanded CD34(+) myeloid progenitors target the inflamed central nervous system (CNS) while keeping their immature phenotype. Based on these results, we then assessed whether CD34(+)/B220(+) cells display in vitro differentiation potential toward microglia. For this purpose, CD34(+)/B220(+) cells were sorted from M-CSF-stimulated bone marrow (BM) cultures and exposed to a glial cell conditioned medium. Under these experimental conditions, CD34(+)/B220(+) cells were able to differentiate into microglial-like cells showing the morphological and phenotypic features of native microglia. Overall, our data suggest that under developmental or neuroinflammatory conditions, a subpopulation of microglial cells derive from CNS-invading CD34(+)/B220(+) myeloid progenitors.
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