How to make an oligodendrocyte

Abstract

Oligodendrocytes produce myelin, an insulating sheath required for the saltatory conduction of electrical impulses along axons. Oligodendrocyte loss results in demyelination, which leads to impaired neurological function in a broad array of diseases ranging from pediatric leukodystrophies and cerebral palsy, to multiple sclerosis and white matter stroke. Accordingly, replacing lost oligodendrocytes, whether by transplanting oligodendrocyte progenitor cells (OPCs) or by mobilizing endogenous progenitors, holds great promise as a therapeutic strategy for the diseases of central white matter. In this Primer, we describe the molecular events regulating oligodendrocyte development and how our understanding of this process has led to the establishment of methods for producing OPCs and oligodendrocytes from embryonic stem cells and induced pluripotent stem cells, as well as directly from somatic cells. In addition, we will discuss the safety of engrafted stem cell-derived OPCs, as well as approaches by which to modulate their differentiation and myelinogenesis in vivo following transplantation.

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

“…Nonetheless, molecular tools to distinguish the cellular subtypes or stages of the oligodendrocyte lineage are lacking. Currently, we are largely restricted to the discrimination of oligodendrocyte progenitor cells from mature oligodendrocytes in the human brain (37)(38)(39). ENPP6 has recently been used as a marker to track the formation of newly formed oligodendrocytes in mice (9); however, it may not be suitable for this purpose in human tissue sections, as demonstrated in the present work.…”

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

“…OPCs differentiate in mature or myelinizing oligodendrocyte, fixing extensions in axons to generate the concentric membrane layers to produce myelin. The presence of oligodendrocytes is more common in the white matter of neuronal tissue, such as the corpus callosum and cerebellum, and less frequent in gray [72]. In both compartments, myelin is necessary for the saltatory conduction of action potentials along axons [73].…”

Recent achievements in stem cell-mediated myelin repair

“…iPSC-dependent oligodendrogenesis was shown to include a radialglia intermediate step as revealed by the expression of paired box protein 6 followed by a transition into OLIG2-positive and NKX2.2-positive cells, massive cell proliferation and subsequent expression of myelin proteins [98]. However, the generation of human iPSC-derived oligodendroglia is timeconsuming and first protocols employed 200 days of culturing before myelin markers were expressed [99]. Despite this technical drawback, such cells were nevertheless shown to generate myelin-forming oligodendrocytes upon transplantation into demyelinated lesions [100,101].…”