Research ArticleMultiple Sclerosis

BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions

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Science Translational Medicine  06 Dec 2017:
Vol. 9, Issue 419, eaam7816
DOI: 10.1126/scitranslmed.aam7816

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Mapping active myelination with BCAS1

Neuronal axon demyelination causes motor and cognitive impairments in multiple sclerosis (MS) and other demyelinating disorders. Although remyelinating strategies have been proposed, the lack of markers to detect areas of active myelination hampers the development of effective therapies. Fard et al. show that myelinating oligodendrocytes constitute a unique population expressing breast carcinoma amplified sequence 1 (BCAS1) in rodent and human brain tissue. In brain samples from deceased MS patients, BCAS1+ cells are present around lesions, suggesting that remyelination might occur during MS and that BCAS1 expression could be used to track responses to remyelinating compounds for treating demyelinating disorders.

Abstract

Investigations into brain function and disease depend on the precise classification of neural cell types. Cells of the oligodendrocyte lineage differ greatly in their morphology, but accurate identification has thus far only been possible for oligodendrocyte progenitor cells and mature oligodendrocytes in humans. We find that breast carcinoma amplified sequence 1 (BCAS1) expression identifies an oligodendroglial subpopulation in the mouse and human brain. These cells are newly formed, myelinating oligodendrocytes that segregate from oligodendrocyte progenitor cells and mature oligodendrocytes and mark regions of active myelin formation in development and in the adult. We find that BCAS1+ oligodendrocytes are restricted to the fetal and early postnatal human white matter but remain in the cortical gray matter until old age. BCAS1+ oligodendrocytes are reformed after experimental demyelination and found in a proportion of chronic white matter lesions of patients with multiple sclerosis (MS) even in a subset of patients with advanced disease. Our work identifies a means to map ongoing myelin formation in health and disease and presents a potential cellular target for remyelination therapies in MS.

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