The reaction of glial cells to brain injury - a new source of neuronal stem cells?
Specific types of glial cells – the radial glia – act as neural stem and progenitor cells in the developing and adult vertebrate brains. However, these are highly specialized glial cells, e.g. possessing epithelial polarity. Here I will discuss a novel source of neural stem cells – namely astroglial cells that resume or acquire stem cell properties only after invasive brain injury. Astrocytes react to a wide range of acute and chronic brain injury and this reaction is typically characterized by hypertrophy and up-regulation of various proteins, including GFAP and nestin. In addition, upon stab wound injury, a considerable proportion of astrocytes resume cell division and some even acquire the potential to form self-renewing and multipotent neurospheres in vitro, as shown by genetic fate mapping (Robel et al., Nature Reviews Neuroscience 2011). Interestingly, this ‘stem cell reaction of reactive astrocytes’ is present after stab wound injury and stroke but remains rather limited in mouse models of amyloidosis, wide-spread non-invasive neuronal death. In the latter reactive astrocytes also did not reactivate proliferation in vivo, nor form any neurospheres in vitro, despite a profound activation and hypertrophy of astrocytes, as well as highly activated microglia. I will then further discuss the molecular signals responsible for the stem cell reaction of astrocytes/glia after brain injury including their source. I will further describe the very first 2Photon live imaging of astrocytes reacting to stab wound injury by repetitive chronic imaging over weeks through a cranial window in vivo. This revealed that only a subpopulation of astrocytes divide and virtually all of them (90%) are located at juxtavascular positions with their somata in direct vicinity of blood vessels. Notably, other astrocytes reacted by polarization towards the injury site and most became hypertrophic, implying an intriguing heterogeneity in astrocyte reaction to this type of injury. Taken together, we identified a novel subset of astrocytes with stem cell potential residing in a vascular niche – as neural stem cells in the zones of adult neurogenesis.
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Location : Université Paris Descartes, Salle des Conférences (2nd floor, room 229), 45 rue des Saints-Pères, 75006 Paris at 11h30