Dynamic spatiotemporal activation of a pervasive neurogenic competence in striatal astrocytes supports continuous neurogenesis following injury

Abstract

Adult neural stem cells (NSCs) are conventionally regarded as rare cells restricted to two niches: the subventricular zone (SVZ) and the subgranular zone. Parenchymal astrocytes (AS) can also contribute to neurogenesis after injury, however the prevalence, distribution, and behaviour of these latent NSCs remained elusive. To tackle these issues, we reconstructed the spatiotemporal pattern of striatal (STR) AS neurogenic activation after excitotoxic lesion in mice. Our results indicate that neurogenic potential is widespread among STR AS but is focally activated at the lesion border, where it associates with different reactive AS subtypes. In this region, similarly to canonical niches, steady state neurogenesis is ensured by the continuous stochastic activation of local AS. Activated AS quickly return to quiescence, while their progeny transiently expand following a stochastic behaviour that features an acceleration in differentiation propensity. Notably, STR AS activation rate matches that of SVZ AS indicating a comparable prevalence of NSC potential.

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ORCID for Philip Greulich: orcid.org/0000-0001-5247-6738

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