http://www.sciencedirect.com/science/article/pii/S2211124715005501
- Under a Creative Commons license
Highlights
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- Programming hippocampal NSPCs into oligodendrocytes follows developmental programs
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- Programming NSPCs into oligodendrocytes enhances remyelination after injury
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- Induced oligodendrocytes mature and myelinate, as shown at a single-cell level
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- Proof of concept for targeting hippocampal NSPCs for glial brain repair is provided
Summary
Demyelinating
diseases are characterized by a loss of oligodendrocytes leading to
axonal degeneration and impaired brain function. Current strategies used
for the treatment of demyelinating disease such as multiple sclerosis
largely rely on modulation of the immune system. Only limited treatment
options are available for treating the later stages of the disease, and
these treatments require regenerative therapies to ameliorate the
consequences of oligodendrocyte loss and axonal impairment. Directed
differentiation of adult hippocampal neural stem/progenitor cells
(NSPCs) into oligodendrocytes may represent an endogenous source of
glial cells for cell-replacement strategies aiming to treat
demyelinating disease. Here, we show that Ascl1-mediated conversion of
hippocampal NSPCs into mature oligodendrocytes enhances remyelination in
a diphtheria-toxin (DT)-inducible, genetic model for demyelination.
These findings highlight the potential of targeting hippocampal NSPCs
for the treatment of demyelinated lesions in the adult brain.
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