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Bhatia, H.S. ; Brunner, A.D.* ; Öztürk, F. ; Kapoor, S. ; Rong, Z. ; Mai, H. ; Thielert, M.* ; Ali, M. ; Al-Maskari, R.* ; Paetzold, J.C. ; Kofler, F. ; Todorov, M.I. ; Molbay, M. ; Kolabas, Z.I. ; Negwer, M. ; Höher, L. ; Steinke, H.* ; Dima, A.* ; Gupta, B. ; Kaltenecker, D. ; Caliskan, Ö.S. ; Brandt, D. ; Krahmer, N. ; Müller, S.* ; Lichtenthaler, S.F.* ; Hellal, F. ; Bechmann, I.* ; Menze, B.* ; Theis, F.J. ; Mann, M.* ; Ertürk, A.

Spatial proteomics in three-dimensional intact specimens.

Cell 185, 5040-5058.e19 (2022)
Free by publisher: Verlagsversion online verfügbar 01/2024
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]
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ai ; Alzheimer's ; Deep Learning ; Human Heart ; Mass Spectrometry ; Proteomics ; Robotics ; Spatial-omics ; Tbi ; Tissue Clearing
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Zeitschrift Cell
Quellenangaben Band: 185, Heft: 26, Seiten: 5040-5058.e19 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed