Levings Daniel C, Pathak Salil Saurav, Yang Yi-Mei, Slattery Matthew
Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
bioRxiv. 2023 May 9:2023.05.09.540014. doi: 10.1101/2023.05.09.540014.
Nrf2 is a broadly expressed transcription factor that regulates gene expression in response to reactive oxygen species (ROS) and oxidative stress. It is commonly referred to as a ubiquitous pathway, but this generalization overlooks work indicating that Nrf2 is essentially unexpressed in some neuronal populations. To explore whether this pattern extends throughout the central nervous system (CNS), we quantified expression and chromatin accessibility at the locus across multiple single cell datasets. In both the mouse and human CNS, was repressed in almost all mature neurons, but highly expressed in non-neuronal support cells, and this pattern was robust across multiple human CNS diseases. A subset of key Nrf2 target genes, like , also remained low in neurons. Thus, these data suggest that while most cells express Nrf2, with activity determined by ROS levels, neurons actively avoid Nrf2 activity by keeping expression low.
Nrf2是一种广泛表达的转录因子，可响应活性氧（ROS）和氧化应激调节基因表达。它通常被称为一种普遍存在的途径，但这种概括忽略了表明Nrf2在某些神经元群体中基本未表达的研究。为了探究这种模式是否在整个中枢神经系统（CNS）中普遍存在，我们在多个单细胞数据集中对该基因座的表达和染色质可及性进行了量化。在小鼠和人类中枢神经系统中，该基因在几乎所有成熟神经元中均受到抑制，但在非神经元支持细胞中高度表达，并且这种模式在多种人类中枢神经系统疾病中都很稳定。Nrf2的一组关键靶基因，如该基因，在神经元中的表达也仍然很低。因此，这些数据表明，虽然大多数细胞表达Nrf2，其活性由ROS水平决定，但神经元通过保持该基因低表达来主动避免Nrf2的活性。
