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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.
Afiliação
  • Bhatia HS; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany.
  • Brunner AD; Department for Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; Boehringer Ingelheim Pharma GmbH & Co. KG, Drug Discovery Sciences, Birkendorfer Str. 65, D-88400 Biberach Riss, Germany.
  • Öztürk F; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Kapoor S; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Rong Z; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany; Munich Medical Research School (MMRS),
  • Mai H; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany; Munich Medical Research School (MMRS),
  • Thielert M; Department for Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
  • Ali M; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Graduate School of Neuroscience (GSN), 82152 Munich, Germany.
  • Al-Maskari R; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany; Center for Translational Cancer Research (TranslaTUM) of the TUM, 81675 Munich, Germany; Image-Based Biomedical Modeling, Department of Informatics, Technical Un
  • Paetzold JC; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Center for Translational Cancer Research (TranslaTUM) of the TUM, 81675 Munich, Germany; Image-Based Biomedical Modeling, Department of Informatics, Technical University of Muni
  • Kofler F; Center for Translational Cancer Research (TranslaTUM) of the TUM, 81675 Munich, Germany; Image-Based Biomedical Modeling, Department of Informatics, Technical University of Munich, 85748 Garching, Germany; Helmholtz AI, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Department of Neuroradiolo
  • Todorov MI; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany.
  • Molbay M; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany; Munich Medical Research School (MMRS),
  • Kolabas ZI; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany; Graduate School of Neuroscience (GSN),
  • Negwer M; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Hoeher L; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Steinke H; Institute of Anatomy, University of Leipzig, 04109 Leipzig, Germany.
  • Dima A; Center for Translational Cancer Research (TranslaTUM) of the TUM, 81675 Munich, Germany; Image-Based Biomedical Modeling, Department of Informatics, Technical University of Munich, 85748 Garching, Germany.
  • Gupta B; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • Kaltenecker D; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany; Institute for Diabetes and Cancer, Helmholz Zentrum München, 85764 Neuherberg, Germany.
  • Caliskan ÖS; Institute for Diabetes and Obesity, Helmholz Zentrum München, 85764 Neuherberg, Germany; German Center for Diabetes Research, Helmholz Zentrum München, 85764 Neuherberg, Germany.
  • Brandt D; Institute for Diabetes and Obesity, Helmholz Zentrum München, 85764 Neuherberg, Germany; German Center for Diabetes Research, Helmholz Zentrum München, 85764 Neuherberg, Germany.
  • Krahmer N; Institute for Diabetes and Obesity, Helmholz Zentrum München, 85764 Neuherberg, Germany; German Center for Diabetes Research, Helmholz Zentrum München, 85764 Neuherberg, Germany.
  • Müller S; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Neuroproteomics, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
  • Lichtenthaler SF; Graduate School of Neuroscience (GSN), 82152 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Neuroproteomics, School of Medicine, Klinikum Rechts der Isar, Technical University of Muni
  • Hellal F; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany.
  • Bechmann I; Institute of Anatomy, University of Leipzig, 04109 Leipzig, Germany.
  • Menze B; Center for Translational Cancer Research (TranslaTUM) of the TUM, 81675 Munich, Germany; Image-Based Biomedical Modeling, Department of Informatics, Technical University of Munich, 85748 Garching, Germany; Department for Quantitative Biomedicine, University of Zurich, 8006 Zurich, Switzerland.
  • Theis F; Institute of Computational Biology, Helmholz Zentrum München, 85764 Neuherberg, Germany; TUM School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany; Department of Mathematics, Technical University of Munich, 85748 Garching, Germany.
  • Mann M; Department for Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: mmann@biochem.mpg.de.
  • Ertürk A; Insititute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, 81377 Munich, Germany; Graduate School of Neuroscience (GSN),
Cell ; 185(26): 5040-5058.e19, 2022 12 22.
Article em En | MEDLINE | ID: mdl-36563667
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Doença de Alzheimer Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoma / Doença de Alzheimer Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article