Spatial proteomics in three-dimensional intact specimens

Bhatia HS, Brunner AD, Oeztuerk F, Kapoor S, Rong Z, Mai H, Thielert M, Ali M, Al-Maskari R, Paetzold JC, Kofler F, Todorov MI, Molbay M, Kolabas ZI, Negwer M, Hoeher L, Steinke H, Dima A, Gupta B, Kaltenecker D, Caliskan OS, Brandt D, Krahmer N, Mueller S, Lichtenthaler SF, Hellal F, Bechmann I, Menze B, Theis F, Mann M, Ertuerk A (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Elsevier

Book Volume: 185

Pages Range: 5040-5058.e19

Journal Issue: 26

DOI: 10.1016/j.cell.2022.11.021

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/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: [Figure presented]

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Universität Leipzig DE Germany (DE)

How to cite

APA:

Bhatia, H.S., Brunner, A.-D., Oeztuerk, F., Kapoor, S., Rong, Z., Mai, H.,... Ertuerk, A. (2022). Spatial proteomics in three-dimensional intact specimens. Cell, 185(26), 5040-5058.e19. https://doi.org/10.1016/j.cell.2022.11.021

MLA:

Bhatia, Harsharan Singh, et al. "Spatial proteomics in three-dimensional intact specimens." Cell 185.26 (2022): 5040-5058.e19.

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