Abstract (Expand)
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/whole-organism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultra-high-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. VIDEO ABSTRACT.
Authors: H. S. Bhatia, A. D. Brunner, F. Ozturk, S. Kapoor, Z. Rong, H. Mai, M. Thielert, M. Ali, R. Al-Maskari, J. C. Paetzold, F. Kofler, M. I. Todorov, M. Molbay, Z. I. Kolabas, M. Negwer, L. Hoeher, H. Steinke, A. Dima, B. Gupta, D. Kaltenecker, O. S. Caliskan, D. Brandt, N. Krahmer, S. Muller, S. F. Lichtenthaler, F. Hellal, I. Bechmann, B. Menze, F. Theis, M. Mann, A. Erturk
Date Published: 22nd Dec 2022
Publication Type: Journal
PubMed ID: 36563667
Citation: Cell. 2022 Dec 22;185(26):5040-5058.e19. doi: 10.1016/j.cell.2022.11.021.
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