Spatial proteomics in three-dimensional intact specimens
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Spatial proteomics in three-dimensional intact specimens. / 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.
In: Cell, Vol. 185, No. 26, 2022, p. 5040-5058.e19.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Spatial proteomics in three-dimensional intact specimens
AU - Bhatia, Harsharan Singh
AU - Brunner, Andreas-David
AU - Öztürk, Furkan
AU - Kapoor, Saketh
AU - Rong, Zhouyi
AU - Mai, Hongcheng
AU - Thielert, Marvin
AU - Ali, Mayar
AU - Al-Maskari, Rami
AU - Paetzold, Johannes Christian
AU - Kofler, Florian
AU - Todorov, Mihail Ivilinov
AU - Molbay, Muge
AU - Kolabas, Zeynep Ilgin
AU - Negwer, Moritz
AU - Hoeher, Luciano
AU - Steinke, Hanno
AU - Dima, Alina
AU - Gupta, Basavdatta
AU - Kaltenecker, Doris
AU - Caliskan, Özüm Sehnaz
AU - Brandt, Daniel
AU - Krahmer, Natalie
AU - Müller, Stephan
AU - Lichtenthaler, Stefan Frieder
AU - Hellal, Farida
AU - Bechmann, Ingo
AU - Menze, Bjoern
AU - Theis, Fabian
AU - Mann, Matthias
AU - Ertürk, Ali
N1 - Copyright © 2022 Elsevier Inc. All rights reserved.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Mice
KW - Humans
KW - Animals
KW - Proteome/analysis
KW - Proteomics/methods
KW - Alzheimer Disease/pathology
KW - Amyloid beta-Peptides
KW - Mass Spectrometry
KW - Plaque, Amyloid
U2 - 10.1016/j.cell.2022.11.021
DO - 10.1016/j.cell.2022.11.021
M3 - Journal article
C2 - 36563667
VL - 185
SP - 5040-5058.e19
JO - Cell
JF - Cell
SN - 0092-8674
IS - 26
ER -
ID: 331590588