title: Bone marrow CD34+/B220+ progenitors target the inflamed brain and display in vitro differentiation potential toward microglia.
abstract: 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.
authors.affiliation: INSERM U433, IFR des Neurosciences de Lyon, Faculté de Médecine Laënnec, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Davoust
authors.forename: C
authors.initials: C
authors.lastname: Vuaillat
authors.forename: G
authors.initials: G
authors.lastname: Cavillon
authors.forename: C
authors.initials: C
authors.lastname: Domenget
authors.forename: E
authors.initials: E
authors.lastname: Hatterer
authors.forename: A
authors.initials: A
authors.lastname: Bernard
authors.forename: C
authors.initials: C
authors.lastname: Dumontel
authors.forename: P
authors.initials: P
authors.lastname: Jurdic
authors.forename: C
authors.initials: C
authors.lastname: Malcus
authors.forename: C
authors.initials: C
authors.lastname: Confavreux
authors.forename: M F
authors.initials: MF
authors.lastname: Belin
authors.forename: S
authors.initials: S
authors.lastname: Nataf
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D001921:Brain / Q000254:growth & development / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D007249:Inflammation / Q000473:pathology*; D017493:Leukocyte Common Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology*
chemical_list: D018952:Antigens, CD34; D017493:Leukocyte Common Antigens