期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.68000
关键词
neurogenesis; hippocampus; stem cell; aging; Human; Mouse
类别
资金
- European Research Council
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung [BSCGI0_157859, 310030_196869, 310030_192622]
- European Research Council [ERC-2019-AdG-885579]
- Swiss National Science Foundation (SNF) [310030_192622, 310030_196869] Funding Source: Swiss National Science Foundation (SNF)
Advancing age leads to decreased hippocampal neurogenesis, which is associated with age-related cognitive decline. The reorganization of the dentate gyrus (DG) niche and changes in the cell-type contributions to the blood-brain barrier and microenvironments surrounding neural stem cells (NSCs) play a pivotal role in maintaining neurogenic permissiveness.
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.
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