Spatial proteomics in three-dimensional intact specimens

被引：67

作者：

Bhatia, Harsharan Singh ^{[1
,2
]}

Brunner, Andreas-David ^{[3
,4
]}

Oeztuerk, Furkan ^{[1
]}

Kapoor, Saketh ^{[1
]}

Rong, Zhouyi ^{[1
,2
,13
]}

Mai, Hongcheng ^{[1
,2
,13
]}

Thielert, Marvin ^{[3
]}

Ali, Mayar ^{[1
,5
]}

Al-Maskari, Rami ^{[2
,7
,8
]}

Paetzold, Johannes Christian ^{[1
,7
,8
,10
]}

Kofler, Florian ^{[7
,8
,9
,12
]}

Todorov, Mihail Ivilinov ^{[1
,2
]}

Molbay, Muge ^{[1
,2
,13
]}

Kolabas, Zeynep Ilgin ^{[1
,2
,5
]}

Negwer, Moritz ^{[1
]}

Hoeher, Luciano ^{[1
]}

Steinke, Hanno

Dima, Alina ^{[7
,8
]}

Gupta, Basavdatta ^{[1
]}

Kaltenecker, Doris ^{[2
,14
]}

Caliskan, Ozum Sehnaz ^{[15
,16
]}

Brandt, Daniel ^{[15
,16
]}

Krahmer, Natalie ^{[15
,16
]}

Mueller, Stephan ^{[17
,18
]}

Lichtenthaler, Stefan Frieder ^{[5
,6
,17
,18
]}

Hellal, Farida ^{[1
,2
]}

Bechmann, Ingo ^{[19
]}

Menze, Bjoern ^{[7
,8
,11
]}

Theis, Fabian ^{[20
,21
,22
]}

Mann, Matthias ^{[3
,23
]}

Ertuerk, Ali ^{[1
,2
,5
,6
]}

机构：

[1] Helmholtz Zentrum Munchen, Inst Tissue Engn & Regenerat Med iTERM, D-85764 Neuherberg, Germany

[2] Ludwig Maximilians Univ Munchen, Klinikum Univ Munchen, Inst Stroke & Dementia Res, D-81377 Munich, Germany

[3] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[4] Boehringer Ingelheim Pharma GmbH & Co KG, Drug Discovery Sci, Birkendorfer Str 65, D-88400 Biberach, Germany

[5] Grad Sch Neurosci GSN, D-82152 Munich, Germany

[6] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany

[7] TUM, Ctr Translat Canc Res TranslaTUM, D-81675 Munich, Germany

[8] Tech Univ Munich, Dept Informat, Image Based Biomed Modeling, D-85748 Garching, Germany

[9] Helmholtz Zentrum Munchen, Helmholtz AI, D-85764 Neuherberg, Germany

[10] Imperial Coll London, Dept Comp, Biomed Image Anal Grp, London SW7 2AZ, England

[11] Univ Zurich, Dept Quantitat Biomed, CH-8006 Zurich, Switzerland

[12] Klinikum Rechts Der Isar, Dept Neuroradiol, D-81675 Munich, Germany

[13] Munich Med Res Sch MMRS, D-80336 Munich, Germany

[14] Helmholz Zentrum Munchen, Inst Diabet & Canc, D-85764 Neuherberg, Germany

[15] Helmholz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany

[16] Helmholz Zentrum Munchen, Ctr Diabet Res, D-85764 Neuherberg, Germany

[17] German Ctr Neurodegenerat Dis DZNE, D-81377 Munich, Germany

[18] Tech Univ Munich, Sch Med, Neuroprote, Klinikum Rechts Isar, D-81675 Munich, Germany

[19] Univ Leipzig, Inst Anat, D-04109 Leipzig, Germany

[20] Helmholz Zentrum Munchen, Inst Computat Biol, D-85764 Neuherberg, Germany

[21] Tech Univ Munich, TUM Sch Life Sci Weihenstephan, D-85354 Freising Weihenstephan, Germany

[22] Tech Univ Munich, Dept Math, D-85748 Garching, Germany

[23] Univ Copenhagen, NNF Ctr Prot Res, Fac Hlth Sci, DK-2200 Copenhagen, Denmark

来源：

CELL | 2022年 / 185卷 / 26期

关键词：

ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; GENE-EXPRESSION; MOUSE MODEL; A-BETA; BRAIN; CELLS; NORMALIZATION; RESOLUTION; PLATFORM;

D O I：

10.1016/j.cell.2022.11.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：5040 / +

页数：39

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