Ion mobility-based sterolomics reveals spatially and temporally distinctive sterol lipids in the mouse brain

Tongzhou Li, Yandong Yin, Zhiwei Zhou, Jiaqian Qiu, Wenbin Liu, Xueting Zhang, Kaiwen He, Yuping Cai and Zheng-Jiang Zhu ()
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Tongzhou Li: Chinese Academy of Sciences
Yandong Yin: Chinese Academy of Sciences
Zhiwei Zhou: Chinese Academy of Sciences
Jiaqian Qiu: Chinese Academy of Sciences
Wenbin Liu: Chinese Academy of Sciences
Xueting Zhang: Chinese Academy of Sciences
Kaiwen He: Chinese Academy of Sciences
Yuping Cai: Chinese Academy of Sciences
Zheng-Jiang Zhu: Chinese Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Aberrant sterol lipid metabolism is associated with physiological dysfunctions in the aging brain and aging-dependent disorders such as neurodegenerative diseases. There is an unmet demand to comprehensively profile sterol lipids spatially and temporally in different brain regions during aging. Here, we develop an ion mobility-mass spectrometry based four-dimensional sterolomics technology leveraged by a machine learning-empowered high-coverage library (>2000 sterol lipids) for accurate identification. We apply this four-dimensional technology to profile the spatially resolved landscapes of sterol lipids in ten functional regions of the mouse brain, and quantitatively uncover ~200 sterol lipids uniquely distributed in specific regions with concentrations spanning up to 8 orders of magnitude. Further spatial analysis pinpoints age-associated differences in region-specific sterol lipid metabolism, revealing changes in the numbers of altered sterol lipids, concentration variations, and age-dependent coregulation networks. These findings will contribute to our understanding of abnormal sterol lipid metabolism and its role in brain diseases.

Date: 2021
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DOI: 10.1038/s41467-021-24672-x

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