Life Sciences Research Unit, University of Luxembourg, Esch-sur-Alzette, Luxembourg; NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg.
Life Sciences Research Unit, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Prog Neurobiol. 2019 Mar;174:36-52. doi: 10.1016/j.pneurobio.2018.12.007. Epub 2018 Dec 29.
Astrocytes play a significant role in coordinating neural development and provide critical support for the function of the CNS. They possess important adaptation capacities that range from their transition towards reactive astrocytes to their ability to undergo reprogramming, thereby revealing their potential to retain latent features of neural progenitor cells. We propose that the mechanisms underlying reactive astrogliosis or astrocyte reprogramming provide an opportunity for initiating neuronal regeneration, a process that is notably reduced in the mammalian nervous system throughout evolution. Conversely, this plasticity may also affect normal astrocytic functions resulting in pathologies ranging from neurodevelopmental disorders to neurodegenerative diseases and brain tumors. We postulate that epigenetic mechanisms linking extrinsic cues and intrinsic transcriptional programs are key factors to maintain astrocyte identity and function, and critically, to control the balance of regenerative and degenerative activity. Here, we will review the main evidences supporting this concept. We propose that unravelling the epigenetic and transcriptional mechanisms underlying the acquisition of astrocyte identity and plasticity, as well as understanding how these processes are modulated by the local microenvironment under specific threatening or pathological conditions, may pave the way to new therapeutic avenues for several neurological disorders including neurodegenerative diseases and brain tumors of astrocytic lineage.
星形胶质细胞在协调神经发育中发挥重要作用，并为中枢神经系统的功能提供关键支持。它们具有重要的适应能力，从反应性星形胶质细胞的转变到能够进行重编程，从而揭示了它们保留神经祖细胞潜在特征的能力。我们提出，反应性星形胶质细胞增生或星形胶质细胞重编程的机制为启动神经元再生提供了机会，而在进化过程中，哺乳动物神经系统中的这一过程显著减少。相反，这种可塑性也可能影响正常星形胶质细胞的功能，导致从神经发育障碍到神经退行性疾病和脑肿瘤等各种疾病。我们假设，将外在线索与内在转录程序联系起来的表观遗传机制是维持星形胶质细胞特性和功能的关键因素，并且对于控制再生和退化活动的平衡至关重要。在这里，我们将回顾支持这一概念的主要证据。我们提出，揭示获得星形胶质细胞特性和可塑性的表观遗传和转录机制，以及了解这些过程如何在特定威胁或病理条件下被局部微环境所调节，可能为包括神经退行性疾病和星形胶质细胞谱系的脑肿瘤在内的几种神经疾病开辟新的治疗途径。
