Spatial proteomics in three-dimensional intact specimens

Bhatia, Harsharan Singh; Brunner, Andreas-David; Oeztuerk, Furkan; Kapoor, Saketh; Rong, Zhouyi; Mai, Hongcheng; Thielert, Marvin; Ali, Mayar; Al-Maskari, Rami; Paetzold, Johannes Christian; Kofler, Florian; Todorov, Mihail Ivilinov; Molbay, Muge; Kolabas, Zeynep Ilgin; Negwer, Moritz; Hoeher, Luciano; Steinke, Hanno; Dima, Alina; Gupta, Basavdatta; Kaltenecker, Doris; Caliskan, Ozum Sehnaz; Brandt, Daniel; Krahmer, Natalie; Mueller, Stephan; Lichtenthaler, Stefan Frieder; Hellal, Farida; Bechmann, Ingo; Menze, Bjoern; Theis, Fabian; Mann, Matthias und Ertuerk, Ali (2022): Spatial proteomics in three-dimensional intact specimens. In: Cell, Bd. 185, Nr. 26: S. 5040-5058

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0092-8674
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198