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纹状体星形胶质细胞中普遍存在的神经发生能力的动态时空激活支持损伤后的持续神经发生。

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

机构信息

Neuroscience Institute Cavalieri Ottolenghi, Orbassano (Turin), Italy; Department of Life Sciences and System Biology, University of Turin, Turin, Italy.

Neuroscience Institute Cavalieri Ottolenghi, Orbassano (Turin), Italy; Department of Neurosciences "Rita Levi Montalcini", University of Turin, Turin, Italy.

出版信息

Stem Cell Reports. 2024 Oct 8;19(10):1432-1450. doi: 10.1016/j.stemcr.2024.08.006. Epub 2024 Sep 19.

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 (ASs) can also contribute to neurogenesis after injury; however, the prevalence, distribution, and behavior 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 ASs 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 ASs. Activated ASs quickly return to quiescence, while their progeny transiently expand following a stochastic behavior that features an acceleration in differentiation propensity. Notably, STR AS activation rate matches that of SVZ ASs indicating a comparable prevalence of NSC potential.

摘要

成人神经干细胞(NSCs)通常被认为是局限于两个龛位的稀有细胞:脑室下区(SVZ)和颗粒下区。室管膜下区的星形胶质细胞(ASs)在损伤后也可以促进神经发生;然而,这些潜在的 NSCs 的普遍性、分布和行为仍然难以捉摸。为了解决这些问题,我们在小鼠兴奋性损伤后重建了纹状体(STR)AS 神经发生的时空模式。我们的结果表明,神经发生潜能在 STR AS 中广泛存在,但在损伤边界处局部激活,在该边界处与不同的反应性 AS 亚型相关。在这个区域,与经典的龛位一样,稳态神经发生是由局部 AS 的连续随机激活来保证的。激活的 AS 很快恢复静止,而它们的后代在随机行为下短暂扩张,其特征是分化倾向加速。值得注意的是,STR AS 的激活率与 SVZ ASs 相匹配,表明 NSC 潜能的普遍性相当。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6b1/11561465/779c0ef4c5e1/gr1.jpg

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