Department of Stomatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Institute of Neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Stem Cells Dev. 2023 Dec;32(23-24):719-730. doi: 10.1089/scd.2023.0196. Epub 2023 Nov 3.
Neural stem/progenitor cells (NSPCs) are present in the mammalian brain throughout life and are involved in neurodevelopment and central nervous system repair. Although typical epigenetic signatures, including DNA methylation, histone modifications, and microRNAs, play a pivotal role in regulation of NSPCs, several of the epigenetic regulatory mechanisms of NSPCs remain unclear. Thus, defining a novel epigenetic feature of NSPCs is crucial for developing stem cell therapy to address neurologic disorders caused by injury. In this study, we aimed to define the R-loop, a three-stranded nucleic acid structure, as an epigenetic characteristic of NSPCs during neurodevelopment. Our results demonstrated that R-loop levels change dynamically throughout neurodevelopment. Cells with high levels of R-loops consistently decreased and were enriched in the area of neurogenesis. Additionally, these cells costained with SOX2 during neurodevelopment. Furthermore, these cells with high R-loop levels expressed Ki-67 and exhibited a high degree of overlap with the transcriptional activation markers, H3K4me3, ser5, and H3K27ac. These findings suggest that R-loops may serve as an epigenetic feature for transcriptional activation in NSPCs, indicating their role in gene expression regulation and neurogenesis.
神经干细胞/祖细胞（NSPCs）在哺乳动物的整个生命周期中都存在于大脑中，并参与神经发育和中枢神经系统修复。尽管典型的表观遗传特征，包括 DNA 甲基化、组蛋白修饰和 microRNAs，在 NSPCs 的调控中发挥着关键作用，但 NSPCs 的一些表观遗传调控机制仍不清楚。因此，定义 NSPCs 的新的表观遗传特征对于开发干细胞疗法以解决由损伤引起的神经紊乱至关重要。在这项研究中，我们旨在将 R 环（一种三链核酸结构）定义为神经发育过程中 NSPCs 的表观遗传特征。我们的结果表明，R 环水平在神经发育过程中动态变化。具有高 R 环水平的细胞持续减少，并在神经发生区域富集。此外，这些细胞在神经发育过程中与 SOX2 共染色。此外，这些具有高 R 环水平的细胞表达 Ki-67，并与转录激活标志物 H3K4me3、ser5 和 H3K27ac 高度重叠。这些发现表明，R 环可能作为 NSPCs 中转录激活的表观遗传特征，表明它们在基因表达调控和神经发生中的作用。
