Multiplexed protein maps link subcellular organization to cellular states

被引:317
作者
Gut, Gabriele [1 ,2 ]
Herrmann, Markus D. [1 ,3 ]
Pelkmans, Lucas [1 ]
机构
[1] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland
[2] Univ Zurich, Life Sci Zurich Grad Sch, Mol Life Sci PhD Program, Zurich, Switzerland
[3] Univ Zurich, Life Sci Zurich Grad Sch, MD PhD & Syst Biol PhD Program, Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
SINGLET-OXYGEN; INACTIVATION; ENDOCYTOSIS; VARIABILITY; REACTIVITY; ANTIBODIES; CELLS;
D O I
10.1126/science.aar7042
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Obtaining highly multiplexed protein measurements across multiple length scales has enormous potential for biomedicine. Here, we measured, by iterative indirect immunofluorescence imaging (4i), 40-plex protein readouts from biological samples at high-throughput from the millimeter to the nanometer scale. This approach simultaneously captures properties apparent at the population, cellular, and subcellular levels, including microenvironment, cell shape, and cell cycle state. It also captures the detailed morphology of organelles, cytoskeletal structures, nuclear subcompartments, and the fate of signaling receptors in thousands of single cells in situ. We used computer vision and systems biology approaches to achieve unsupervised comprehensive quantification of protein subcompartmentalization within various multicellular, cellular, and pharmacological contexts. Thus, highly multiplexed subcellular protein maps can be used to identify functionally relevant single-cell states.
引用
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页数:13
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共 51 条
[1]   Multiplexed ion beam imaging of human breast tumors [J].
Angelo, Michael ;
Bendall, Sean C. ;
Finck, Rachel ;
Hale, Matthew B. ;
Hitzman, Chuck ;
Borowsky, Alexander D. ;
Levenson, Richard M. ;
Lowe, John B. ;
Liu, Scot D. ;
Zhao, Shuchun ;
Natkunam, Yasodha ;
Nolan, Garry P. .
NATURE MEDICINE, 2014, 20 (04) :436-+
[2]   Control of Transcript Variability in Single Mammalian Cells [J].
Battich, Nico ;
Stoeger, Thomas ;
Pelkmans, Lucas .
CELL, 2015, 163 (07) :1596-1610
[3]   Image-based transcriptomics in thousands of single human cells at single-molecule resolution [J].
Battich, Nico ;
Stoeger, Thomas ;
Pelkmans, Lucas .
NATURE METHODS, 2013, 10 (11) :1127-1133
[4]   Regulation of catalytic activity of S6 kinase 2 during cell cycle [J].
Boyer, Derek ;
Quintanilla, Rene ;
Lee-Fruman, Kay K. .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2008, 307 (1-2) :59-64
[5]   In the right place at the right time: visualizing and understanding mRNA localization [J].
Buxbaum, Adina R. ;
Haimovich, Gal ;
Singer, Robert H. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2015, 16 (02) :95-109
[6]   Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells [J].
Capuani, Fabrizio ;
Conte, Alexia ;
Argenzio, Elisabetta ;
Marchetti, Luca ;
Priami, Corrado ;
Polo, Simona ;
Di Fiore, Pier Paolo ;
Sigismund, Sara ;
Ciliberto, Andrea .
NATURE COMMUNICATIONS, 2015, 6
[7]   CellProfiler: image analysis software for identifying and quantifying cell phenotypes [J].
Carpenter, Anne E. ;
Jones, Thouis Ray ;
Lamprecht, Michael R. ;
Clarke, Colin ;
Kang, In Han ;
Friman, Ola ;
Guertin, David A. ;
Chang, Joo Han ;
Lindquist, Robert A. ;
Moffat, Jason ;
Golland, Polina ;
Sabatini, David M. .
GENOME BIOLOGY, 2006, 7 (10)
[8]   Spatially resolved, highly multiplexed RNA profiling in single cells [J].
Chen, Kok Hao ;
Boettiger, Alistair N. ;
Moffitt, Jeffrey R. ;
Wang, Siyuan ;
Zhuang, Xiaowei .
SCIENCE, 2015, 348 (6233)
[9]   READILY AVAILABLE FLUORESCEIN ISOTHIOCYANATE-CONJUGATED ANTIBODIES CAN BE EASILY CONVERTED INTO TARGETED PHOTOTOXIC AGENTS FOR ANTIBACTERIAL, ANTIVIRAL, AND ANTICANCER THERAPY [J].
DEVANATHAN, S ;
DAHL, TA ;
MIDDEN, WR ;
NECKERS, DC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (08) :2980-2984
[10]   Cell-intrinsic adaptation of lipid composition to local crowding drives social behaviour [J].
Frechin, Mathieu ;
Stoeger, Thomas ;
Daetwyler, Stephan ;
Gehin, Charlotte ;
Battich, Nico ;
Damm, Eva-Maria ;
Stergiou, Lilli ;
Riezman, Howard ;
Pelkmans, Lucas .
NATURE, 2015, 523 (7558) :88-+