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Published on: April 13, 2017
Bone marrow CD34+/B220+ progenitors target the inflamed brain and display in vitro differentiation potential toward
N Davoust1, C Vuaillat, G Cavillon
1INSERM U433, IFR des Neurosciences de Lyon, Faculté de Médecine Laënnec, Lyon, France.
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.
Insights
Microglia may originate from circulating CD34+/B220+ myeloid progenitors, not mature monocytes. These progenitors target the brain during development and neuroinflammation, differentiating into microglial cells.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells are key immune cells in the central nervous system (CNS).
- Their precise origin, particularly whether they derive from circulating monocytes or other progenitor cells, remains debated.
- Recent findings suggest microglial cells may share features with myeloid progenitors.
Purpose of the Study:
- To investigate the hypothesis that microglia, or a subset thereof, originate from circulating CD34+/B220+ myeloid progenitors.
- To determine if these progenitors can target the brain under developmental or neuroinflammatory conditions.
- To assess the differentiation potential of CD34+/B220+ cells into microglial cells.
Main Methods:
- Observation of CD34 and B220 antigen expression on microglial cells during brain development.
- Utilizing experimental allergic encephalomyelitis (EAE) as a model for chronic neuroinflammation.
- Performing intravenous transfer experiments with macrophage-colony stimulating factor (M-CSF)-expanded CD34+ myeloid progenitors in EAE mice.
- In vitro differentiation assays of CD34+/B220+ cells from bone marrow cultures using glial cell conditioned medium.
Main Results:
- A subpopulation of microglial cells expressed CD34 and B220 antigens during brain development.
- In EAE mice, a distinct population of CD34+/B220+ cells was found to expand in both blood and brain.
- Intravenously transferred M-CSF-expanded CD34+ myeloid progenitors successfully targeted the inflamed CNS in EAE mice, retaining an immature phenotype.
- Sorted CD34+/B220+ cells demonstrated in vitro differentiation into microglial-like cells with characteristic morphology and phenotype.
Conclusions:
- Data suggest that a subset of microglial cells originates from CD34+/B220+ myeloid progenitors that invade the CNS.
- These progenitors may play a role in both brain development and neuroinflammatory conditions.
- The findings challenge the traditional view of microglial origins and highlight a potential pathway for immune cell contribution to the brain.
