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Canhos Lange, Luisa; Falk, Sven; Sirko, Swetlana ORCID logoORCID: https://orcid.org/0000-0001-5950-616X and Götz, Magdalena ORCID logoORCID: https://orcid.org/0000-0003-1551-9203 (June 2017): Self-renewal and differentiation potential of reactive astrocytes in vivo. In: Glia, Vol. 65, E121

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Reactive astrogliosis is a reaction of the central nervous system (CNS) common to diverse types of injury, but only upon invasive injury a subset of reactive astrocytes (RAs) acquires proliferative capacity in vivo and exhibits self-renewal and multipotency in vitro, as measured by neurosphere formation (Buffo et al., 2008; Götz et al., 2015; Sirko et al., 2013). Given that in the adult mammalian brain only adult neural stem cells (aNSCs), which are akin to astrocytes, are able to self-renew and give rise to neurons, it is important to test to which extent RAs can enact their NSC potential also in vivo. In this study, we used a variety of in vivo and in vitro experimental models to investigate (i) whether and to which extent RAs in the post-traumatic cerebral cortex grey matter exhibit indeed self-renewal in vivo; (ii) whether RAs can give rise to different cell types in vivo and (iii) to which extent local environment can influence the differentiation potential of RAs. The results of our study demonstrate for the first time that a distinct subset of RAs within the injured parenchyma of cerebral cortex can enter the cell cycle for several times. This was shown by a double EdU and BrdU pulse after repetitive injury and by clonal analysis using GlastCreERT2-mediated recombination in confetti reporter lines. In addition, data will be presented of neurosphere cells derived from RAs grafted in three different neurogenic niches, the adult subependymal zone, the adult subgranular zone and the midneurogenesis cerebral cortex at embryonic day 14. Taken together, our findings advance the concept about proliferation and multilineage potential of reactive astrocytes.

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