Characterization of the neurogenic niche in the aging dentate gyrus using iterative immunofluorescence imaging.
Characterization of the neurogenic niche in the aging dentate gyrus using iterative immunofluorescence imaging.
复制标题
使用迭代免疫荧光成像的衰老齿状回的神经源性生殖位的表征。
DOI：
10.7554/elife.68000
复制
发表时间：
2022-01-28
期刊：
影响因子：
7.7
通讯作者：
Jessberger S
中科院分区：
文献类型：
--
作者：
Cole JD;Sarabia Del Castillo J;Gut G;Gonzalez-Bohorquez D;Pelkmans L;Jessberger S
年龄增长会导致海马神经发生减少，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的局限性，人们对年龄引起的神经干细胞（NSC）和海马微环境内周围细胞变化的空间关系仍然知之甚少。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，以表征 2、6 和 12 个月大小鼠的 NSC 和周围细胞。我们发现中年小鼠中已经发生了齿状回（DG）生态位的重组，与神经发生的下降同时发生。基于 4i 的 DG 组织分析确定了细胞类型对血脑屏障和 NSC 周围微环境的影响的变化，在保持神经源性许可方面发挥着关键作用。所提供的数据代表了一种资源，用于描述导致衰老 DG 内干细胞相关可塑性改变的原理，并提供分析复杂组织中整个生命周期中体干细胞生态位的蓝图。
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.