Casas-Tinto Sergio, Garcia-Guillen Nuria, Losada-Perez María
Instituto Cajal (CSIC), Madrid, Spain.
Instituto de Investigación de Enfermedades Raras (IIER-ISCIII), Majadahonda, Spain.
Elife. 2025 Mar 7;13:RP96890. doi: 10.7554/eLife.96890.
As the global population ages, the prevalence of neurodegenerative disorders is fast increasing. This neurodegeneration as well as other central nervous system (CNS) injuries cause permanent disabilities. Thus, generation of new neurons is the rosetta stone in contemporary neuroscience. Glial cells support CNS homeostasis through evolutionary conserved mechanisms. Upon damage, glial cells activate an immune and inflammatory response to clear the injury site from debris and proliferate to restore cell number. This glial regenerative response (GRR) is mediated by the neuropil-associated glia (NG) in , equivalent to vertebrate astrocytes, oligodendrocytes (OL), and oligodendrocyte progenitor cells (OPCs). Here, we examine the contribution of NG lineages and the GRR in response to injury. The results indicate that NG exchanges identities between ensheathing glia (EG) and astrocyte-like glia (ALG). Additionally, we found that NG cells undergo transdifferentiation to yield neurons. Moreover, this transdifferentiation increases in injury conditions. Thus, these data demonstrate that glial cells are able to generate new neurons through direct transdifferentiation. The present work makes a fundamental contribution to the CNS regeneration field and describes a new physiological mechanism to generate new neurons.
随着全球人口老龄化，神经退行性疾病的患病率正在迅速上升。这种神经退行性变以及其他中枢神经系统（CNS）损伤会导致永久性残疾。因此，新神经元的生成是当代神经科学的关键所在。神经胶质细胞通过进化上保守的机制维持中枢神经系统的稳态。在受到损伤时，神经胶质细胞会激活免疫和炎症反应，以清除损伤部位的碎片，并通过增殖来恢复细胞数量。这种神经胶质再生反应（GRR）由神经毡相关神经胶质（NG）介导，在功能上等同于脊椎动物的星形胶质细胞、少突胶质细胞（OL）和少突胶质细胞前体细胞（OPC）。在这里，我们研究了NG谱系和GRR对损伤的反应。结果表明，NG在包被神经胶质（EG）和星形胶质样神经胶质（ALG）之间交换身份。此外，我们发现NG细胞会发生转分化产生神经元。而且，这种转分化在损伤条件下会增加。因此，这些数据表明神经胶质细胞能够通过直接转分化产生新的神经元。本研究为中枢神经系统再生领域做出了重要贡献，并描述了一种产生新神经元的新生理机制。
