Cell · 2022
Spatial proteomics in three-dimensional intact specimens.
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Bhatia Harsharan Singh, Brunner Andreas-David, Öztürk 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 Özüm Sehnaz, Brandt Daniel, Krahmer Natalie, Müller Stephan, Lichtenthaler Stefan Frieder, Hellal Farida, Bechmann Ingo, Menze Bjoern, Theis Fabian, Mann Matthias, Ertürk Ali
Аннотация
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.