A molecule known as Sox10 enables brain cells called astrocytes to convert into myelin-forming oligodendrocytes, a new study in mice reports. The findings suggest an approach for myelin repair in patients with multiple sclerosis (MS) and similar disorders, its researchers said.
The study, “In vivo conversion of astrocytes into oligodendrocyte lineage cells with transcription factor Sox10; Promise for myelin repair in multiple sclerosis,” was published in the journal PLOS ONE.
Given the key role of oligodendrocyte pathology in MS, replacing these myelin-producing cells would be a promising therapeutic approach, particularly if autologous (of the same individual) sources of oligodendrocyte progenitor cells (OPCs) can be used.
Astrocytes – a cell involved in the formation of the blood-brain barrier and in response to injury – are the major component of glial scars, which develop after neural cell loss caused by degenerative diseases and traumatic injuries.
Prior research has shown that astrocytes may be converted into neurons (nerve cells) and stem-like cells in vitro by forcing the production of transcription factors, or molecules that control gene activity. As a result, changing astrocytes into progenitor cells has been attempted in vivo — inside a living organism — to enable tissue repair.
Both astrocytes and oligodendrocytes are types of glial cells. Astrocytes have been converted into myelinating cells with a micro RNA – tiny RNA molecules that also regulate gene activity – and a transcription factor not specific to oligodendrocytes. This inspired a research team at the Royan Institute for Stem Cell Biology and Technology in Iran and the University of California, Davis, to look for a transcription factor specific to oligodendrocytes that also showed an ability to change astrocytes into OPCs in vivo.
Sox10 is a transcription factor produced constantly throughout oligodendrocyte progenitor cell development into mature oligodendrocytes, and is associated with the activation of myelination genes. In mice, Sox 10 is known to contribute to the generation of OPCs from fibroblasts, the main cells of connective tissues.
To explore the potential of Sox10 to convert astrocytes to oligodendrocytes, the researchers injected modified, harmless viral particles containing Sox10 and a fluorescent tag (to enable detection) into the area that connects the two sides of the brain, called corpus callosum, in mice with experimentally induced demyelination.
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