The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USA.
The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USA; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, N.L. 64710, Mexico.
Cell Rep. 2021 Feb 2;34(5):108721. doi: 10.1016/j.celrep.2021.108721.
Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies. We have studied the molecular changes in the injury environment and the astrocyte-specific responses by astrocyte purification from injured spinal cords from acute to chronic stages. In addition to protein-coding genes, we have systematically analyzed the expression profiles of long non-coding RNAs (lncRNAs) (>200 bp), which are regulatory RNAs that play important roles in the CNS. We have identified a highly conserved lncRNA, Zeb2os, and demonstrated using functional assays that it plays an important role in reactive astrogliosis through the Zeb2os/Zeb2/Stat3 axis. These studies provide valuable insights into the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the function(s) of lncRNAs in astrogliosis and SCI.
脊髓损伤 (SCI) 是一种最具破坏性的神经损伤,目前尚无有效的治疗方法。星形胶质细胞是瘢痕的主要组成部分。了解反应性星形胶质细胞对 SCI 病理生理学的复杂贡献,对于开发治疗策略至关重要。我们通过从急性到慢性阶段从损伤的脊髓中纯化星形胶质细胞,研究了损伤环境中的分子变化和星形胶质细胞特异性反应。除了蛋白编码基因外,我们还系统地分析了长非编码 RNA (lncRNA) (>200 bp) 的表达谱,lncRNA 是在中枢神经系统中发挥重要作用的调节性 RNA。我们鉴定了一个高度保守的 lncRNA,Zeb2os,并通过功能测定表明它通过 Zeb2os/Zeb2/Stat3 轴在反应性星形胶质细胞增生中发挥重要作用。这些研究为反应性星形胶质细胞增生的分子基础提供了有价值的见解,并填补了 lncRNA 在星形胶质细胞增生和 SCI 中的功能方面的知识空白。