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Journal Article

Spatial proteomics in three-dimensional intact specimens

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Brunner,  Andreas-David
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Thielert,  Marvin
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78356

Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Bhatia, H. S., Brunner, A.-D., Oeztuerk, F., Kapoor, S., Rong, Z., Mai, H., et al. (2022). Spatial proteomics in three-dimensional intact specimens. Cell, 185(26), 5040-5058. doi:10.1016/j.cell.2022.11.021.


Cite as: https://hdl.handle.net/21.11116/0000-000C-8680-B
Abstract
Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of large biological specimens imaged in 3D are lacking. Here, we present DISCO-MS, a technology that combines whole-organ/wholeorganism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultrahigh-sensitivity mass spectrometry. DISCO-MS yielded proteome data indistinguishable from uncleared samples in both rodent and human tissues. We used DISCO-MS to investigate microglia activation along axonal tracts after brain injury and characterized early-and late-stage individual amyloid-beta plaques in a mouse model of Alzheimer's disease. DISCO-bot robotic sample extraction enabled us to study the regional heterogeneity of immune cells in intact mouse bodies and aortic plaques in a complete human heart. DISCO-MS enables unbiased proteome analysis of preclinical and clinical tissues after unbiased imaging of entire specimens in 3D, identifying diagnostic and therapeutic opportunities for complex diseases.