Characterization of the neurogenic niche in the aging dentate gyrus using iterative immunofluorescence imaging.
John Darby ColeJacobo Sarabia Del CastilloGabriele GutDaniel Gonzalez-BohorquezLucas PelkmansSebastian JessbergerPublished in: eLife (2022)
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.
Keyphrases
- stem cells
- neural stem cells
- cognitive decline
- induced apoptosis
- cell cycle arrest
- spinal cord injury
- middle aged
- high resolution
- cerebral ischemia
- mild cognitive impairment
- computed tomography
- image quality
- type diabetes
- endoplasmic reticulum stress
- cell death
- machine learning
- big data
- magnetic resonance imaging
- high throughput
- mesenchymal stem cells
- metabolic syndrome
- magnetic resonance
- dna methylation
- diabetic rats
- mass spectrometry
- subarachnoid hemorrhage
- artificial intelligence
- cell therapy
- deep learning
- quantum dots
- cell proliferation
- fluorescence imaging
- contrast enhanced