Spatial proteomics reveals human microglial states shaped by anatomy and neuropathology
Abstract/Contents
- Abstract
- Microglia are implicated in aging, neurodegeneration, and Alzheimer’s disease (AD). Traditional, low-plex, imaging methods fall short of capturing in situ cellular states and interactions in the human brain. We utilized Multiplexed Ion Beam Imaging (MIBI) and data-driven analysis to spatially map proteomic cellular states and niches in healthy human brain, identifying a spectrum of microglial profiles, called the microglial state continuum (MSC). The MSC ranged from senescent-like to active proteomic states that were skewed across large brain regions and compartmentalized locally according to their immediate microenvironments. While more active microglial states were proximal to amyloid plaques, globally, microglia significantly shifted towards a, presumably, dysfunctional low MSC in the AD hippocampus, as confirmed in an independent cohort (n=26). This provides an in situ single cell framework for mapping human microglial states along a continuous, shifting existence that is differentially enriched between healthy brain regions and disease, reinforcing differential microglial functions overall.
Description
| Type of resource | Dataset, still image |
|---|---|
| Publication date | May 30, 2023 |
Creators/Contributors
| Author | Mrdjen, Dunja |
|---|---|
| Author | Amouzgar, Meelad |
| Author | Canon, Bryan |
| Author | Liu, Candace |
| Author | Spence, Angie |
| Author | McCaffrey, Erin |
| Author | Bharadwaj, Anusha |
| Author | Tebaykin, Dmitry |
| Author | Bukhari, Syed |
| Author | Hartmann, Felix |
| Author | Kagel, Adam |
| Author | Vijayaragavan, Kausalia |
| Author | Oliveria, John-Paul |
| Author | Yakabi, Koya |
| Author | Corrada, Maria |
| Author | Kawas, Claudia |
| Author | Camacho, Christine |
| Author | Bosse, Marc |
| Author | Tibshirani, Robert |
| Author | Angelo, Michael |
| Author | Beach, Thomas |
| Author | Montine, Thomas |
| Author | Bendall, Sean |
Subjects
| Subject | Microglia |
|---|---|
| Subject | Aging |
| Subject | Human |
| Subject | Alzheimer's disease |
| Subject | Neuropathologists |
| Subject | Proteomics |
| Subject | Imaging systems in medicine |
| Subject | Neuroimmunology |
| Subject | Multiplexing |
| Subject | Machine learning |
| Subject | Spatial analysis (Statistics) |
| Genre | Data |
| Genre | Image |
| Genre | Data sets |
| Genre | Dataset |
Bibliographic information
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution 4.0 International license (CC BY).
Preferred citation
- Preferred citation
- Mrdjen, D., Amouzgar, M., Canon, B., Liu, C., Spence, A., McCaffrey, E., Bharadwaj, A., Tebaykin, D., Bukhari, S., Hartmann, F., Kagel, A., Vijayaragavan, K., Oliveria, J., Yakabi, K., Corrada, M., Kawas, C., Camacho, C., Bosse, M., Tibshirani, R., Angelo, M., Beach, T., Montine, T., and Bendall, S. (2023). Spatial proteomics reveals human microglial states shaped by anatomy and neuropathology. Stanford Digital Repository. Available at https://purl.stanford.edu/rb134mq9525. https://doi.org/10.25740/rb134mq9525.
Collection
Stanford Research Data
View other items in this collection in SearchWorksContact information
Also listed in
Loading usage metrics...