在成年鼠脑中,神经干细胞(NSC)可以在两个主要的位置发现:齿状回(DG)和脑室下区(SVZ)。在DG中,NSC产生分化为兴奋性神经元的中间祖细胞(IPs),当SVZ中的祖细胞迁移到嗅球(OB)时,它们主要分化成抑制性中间神经元。神经发生,产生新神经元的过程,持续一生,但随着年龄的增长而急剧下降,伴随着炎症的增加。虽然许多细胞类型,包括小胶质细胞,经历显著的转录变化,在神经祖细胞中很少检测到这种变化。此外,来自不同神经源性区域的祖细胞的转录谱尚未在单细胞水平上进行比较,人们对它们如何受到衰老相关炎症的影响知之甚少。我们已经生成了针对IP的单细胞RNA测序数据集,这表明大多数老化的神经祖细胞只能获得微小的转录变化。然而,将成为兴奋性神经元的祖细胞比其他祖细胞减少得更快。此外,SVZ的老年人群,在OB中未检测到,获得与免疫反应相关的主要转录激活。这表明,区域之间年龄相关的神经源性下降的差异不是由于组织差异,而是由于细胞类型特异性的内在转录程序。SVZ中的神经母细胞亚群对年龄相关的炎症信号有强烈的反应。
In the adult murine brain, neural stem cells (NSCs) can be found in two main niches: the dentate gyrus (DG) and the subventricular zone (SVZ). In the DG, NSCs produce intermediate progenitors (IPs) that differentiate into excitatory neurons, while progenitors in the SVZ migrate to the olfactory bulb (OB), where they mainly differentiate into inhibitory interneurons. Neurogenesis, the process of generating new neurons, persists throughout life but decreases dramatically with aging, concomitantly with increased inflammation. Although many cell types, including microglia, undergo significant transcriptional changes, few such changes have been detected in neural progenitors. Furthermore, transcriptional profiles in progenitors from different neurogenic regions have not been compared on a single-cell level, and little is known about how they are affected by aging-related inflammation. We have generated a single cell RNA sequencing dataset enriched for IPs, which revealed that most aged neural progenitors only acquire minor transcriptional changes. However, progenitors set to become excitatory neurons decrease faster than others. In addition, a population in the aged SVZ, not detected in the OB, acquired major transcriptional activation related to immune responses. This suggests that differences in age related neurogenic decline between regions is not due to tissue differences but rather cell type specific intrinsic transcriptional programs, and that subset of neuroblasts in the SVZ react strongly to age related inflammatory cues.