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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Neuron
2026
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/42276056/ |
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Table of Contents:
- Single-cell proteome atlas of aging mouse microglia reveals subpopulation-specific phagoproteome. Zhang, Haoran Liu, Zhen Chen, Bijia Zhang, Guangxin Wang, Longteng Wei, Changsheng Zhang, Xiaohui Luo, Yuxiang Peng, Ting Fang, Qing Gu, Lei Ge, Ruicheng Zhu, Jiangning Yang, Ruiying Shen, Weiguo Jiang, Zhujun Sun, Yufang Duan, Weixun Liu, Jincheng Li, Tingting Wang, Jing Gao, Zhihua Yu, Xiang Chen, Hebing Ye, Zilu Shi, Xiaomeng Li, Cheng Microglia are brain-resident immune cells with complex physiological functions. Exploring their proteomic heterogeneity at the single-cell level has remained technically challenging. Here, we optimized a label-free single-cell proteomics (SCP) workflow using Orbitrap Astral mass spectrometry (MS) and applied it to fluorescence-activated cell sorting (FACS)-sorted microglia from the hippocampus and prefrontal cortex of young, middle-aged, and aged mice. This yielded one of the largest SCP datasets to date, comprising 3,085 single cells, with an average of 1,153 protein groups identified per cell. Compared with single-cell transcriptomic data, the SCP dataset showed higher expression completeness and moderate cross-modality correlation. This dataset revealed spatiotemporal proteomic heterogeneity of microglia during aging. Notably, we defined the microglial "phagoproteome," uncovering state-specific phagocytic preferences, and verified these results by imaging. This study underscores the potential of SCP to reveal subpopulation-specific proteomic dynamics and provides a new resource for studying microglial state transitions during aging.