Characterizing and enumerating cells of the oligodendrocyte lineage (OLCs) is crucial for understanding demyelination and therapeutic benefit in models of demyelinating disease in the central nervous system. Here we describe a novel method for the rapid, unbiased analysis of mouse OLCs using flow cytometry. The assay was optimized to maximize viable yield of OLCs and maintain OLC antigen integrity. Panels of antibodies were assembled for simultaneous analysis of seven antigens on individual cells allowing for characterization of oligodendroglial cells throughout the lineage. We verified the utility of the assay with cultured OLCs and through a time course of developmental myelination. Next we employed the assay to characterize OLC populations in two well-characterized models of demyelination: cuprizone-induced demyelination and experimental autoimmune encephalomyelitis (EAE). In EAE we observed a dramatic loss of mature oligodendrocytes coincident with a dramatic expansion of oligodendrocyte progenitors cells (OPCs) at the onset of disease suggesting an attempt of the host to repair myelin. This expanded OPC pool was maintained through remission and relapse suggesting an arrest in differentiation in the face of the chronic autoimmune T cell-mediated inflammatory response. These robust, reproducible changes in OLCs through disease provide a rapid quantitative global analysis of myelin-producing cells in the adult mouse brain and important information regarding effects of disease on oligodendroglial proliferation/differentiation which is useful for defining the pathogenesis and therapy of MS.
Pubmed ID: 25247590 RIS Download
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A non-profit foundation that funds basic research and is focused on accelerating the development of myelin repair therapeutics for multiple sclerosis. They have defined a 15-year research plan to develop a drug or drugs and believes its Accelerated Research Collaborative (ARC) model can subsequently be used to accelerate the treatment for all diseases. The ARC framework coordinates and manages the entire therapeutic development continuum from discovery biology to FDA approval. The model works by coordinating multi-disciplinary basic research from academic and government laboratories, systematically validating and derisking potential compounds/targets, and collaborating with pharma partners to increase the probability of successful programs.
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