Brain Research Institute, University of Zurich, Zurich, Switzerland.
Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Elife. 2022 Jan 28;11:e68000. doi: 10.7554/eLife.68000.
Advancing age causes reduced hippocampal neurogenesis, associated with age-related cognitive decline. The spatial relationship of age-induced alterations in neural stem cells (NSCs) and surrounding cells within the hippocampal niche remains poorly understood due to limitations of antibody-based cellular phenotyping. We established iterative indirect immunofluorescence imaging (4i) in tissue sections, allowing for simultaneous detection of 18 proteins to characterize NSCs and surrounding cells in 2-, 6-, and 12-month-old mice. We show that reorganization of the dentate gyrus (DG) niche already occurs in middle-aged mice, paralleling the decline in neurogenesis. 4i-based tissue analysis of the DG identifies changes in cell-type contributions to the blood-brain barrier and microenvironments surrounding NSCs to play a pivotal role to preserve neurogenic permissiveness. The data provided represent a resource to characterize the principles causing alterations of stem cell-associated plasticity within the aging DG and provide a blueprint to analyze somatic stem cell niches across lifespan in complex tissues.
随着年龄的增长,海马神经发生减少,与年龄相关的认知能力下降有关。由于基于抗体的细胞表型分析存在局限性,因此对于海马龛内年龄诱导的神经干细胞(NSC)和周围细胞的空间关系仍知之甚少。我们在组织切片中建立了迭代间接免疫荧光成像(4i),允许同时检测 18 种蛋白质,以鉴定 2、6 和 12 个月大的小鼠中的 NSCs 和周围细胞。我们表明,齿状回(DG)龛位的重新组织已经在中年小鼠中发生,与神经发生的下降平行。基于 4i 的 DG 组织分析确定了对血脑屏障和 NSCs 周围微环境的细胞类型贡献的变化,在维持神经发生的许可方面发挥着关键作用。提供的数据代表了一种资源,可以描述导致衰老 DG 中与干细胞相关的可塑性改变的原则,并为分析复杂组织中整个生命周期的体干细胞龛位提供了蓝图。