Neural Stem Cell Biology Laboratory, The Francis Crick Institute, London, UK.
WIREs Mech Dis. 2022 Sep;14(5):e1557. doi: 10.1002/wsbm.1557. Epub 2022 May 12.
Astrocytes are a major type of glial cells that have essential functions in development and homeostasis of the central nervous system (CNS). Immature astrocytes in the developing CNS support neuronal maturation and possess neural-stem-cell-like properties. Mature astrocytes partially lose these functions but gain new functions essential for adult CNS homeostasis. In pathological conditions, astrocytes become "reactive", which disrupts their mature homeostatic functions and reactivates some immature astrocyte-like properties, suggesting a partial reversal of astrocyte maturation. The loss of homeostatic astrocyte functions contributes to the pathogenesis of various neurological conditions, and therefore activating maturation-promoting mechanisms may be a promising therapeutic strategy to restore homeostasis. Manipulating the mechanisms underlying astrocyte maturation might also allow to facilitate CNS regeneration by enhancing developmental functions of adult astrocytes. However, such therapeutic strategies are still some distance away because of our limited understanding of astrocyte differentiation and maturation, due to biological and technical challenges, including the high degree of similarity of astrocytes with neural stem cells and the shortcomings of astrocyte markers. Current advances in systems biology have a huge potential to overcome these challenges. Recent transcriptomic analyses have already revealed new astrocyte markers and new regulators of astrocyte differentiation. However, the epigenomic changes that presumably occur during astrocyte differentiation remain an important, largely unexplored area for future research. Emerging technologies such as CRISPR/Cas9-based functional screens will further improve our understanding of the mechanisms underlying astrocyte differentiation. This may open up new clinical approaches to restore homeostasis in neurological disorders and/or promote CNS regeneration. This article is categorized under: Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Stem Cells and Development Neurological Diseases > Molecular and Cellular Physiology.
星形胶质细胞是一种主要的神经胶质细胞，在中枢神经系统（CNS）的发育和稳态中具有重要功能。发育中的中枢神经系统中的未成熟星形胶质细胞支持神经元成熟，并具有神经干细胞样特性。成熟的星形胶质细胞部分失去这些功能，但获得了新的、对成年中枢神经系统稳态至关重要的功能。在病理条件下，星形胶质细胞变得“反应性”，这破坏了它们成熟的稳态功能，并重新激活了一些未成熟的星形胶质细胞样特性，表明星形胶质细胞成熟的部分逆转。稳态星形胶质细胞功能的丧失导致各种神经疾病的发病机制，因此激活促进成熟的机制可能是恢复稳态的一种有前途的治疗策略。操纵星形胶质细胞成熟的机制也可能通过增强成年星形胶质细胞的发育功能来促进中枢神经系统的再生。然而，由于我们对星形胶质细胞分化和成熟的理解有限，由于生物学和技术挑战，包括星形胶质细胞与神经干细胞高度相似以及星形胶质细胞标志物的缺点，这种治疗策略仍有一定距离。系统生物学的最新进展具有克服这些挑战的巨大潜力。最近的转录组分析已经揭示了新的星形胶质细胞标志物和新的星形胶质细胞分化调节剂。然而，在星形胶质细胞分化过程中可能发生的表观遗传变化仍然是未来研究的一个重要而尚未探索的领域。新兴技术，如基于 CRISPR/Cas9 的功能筛选，将进一步提高我们对星形胶质细胞分化机制的理解。这可能为恢复神经疾病中的稳态和/或促进中枢神经系统再生开辟新的临床途径。本文归入以下类别： 神经疾病 > 遗传学/基因组学/表观遗传学 神经疾病 > 干细胞与发育 神经疾病 > 分子和细胞生理学。
