Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation. / Brunner, Andreas-David; Thielert, Marvin; Vasilopoulou, Catherine; Ammar, Constantin; Coscia, Fabian; Mund, Andreas; Hoerning, Ole B; Bache, Nicolai; Apalategui, Amalia; Lubeck, Markus; Richter, Sabrina; Fischer, David S; Raether, Oliver; Park, Melvin A; Meier, Florian; Theis, Fabian J; Mann, Matthias.

In: Molecular Systems Biology, Vol. 18, No. 3, e10798, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Brunner, A-D, Thielert, M, Vasilopoulou, C, Ammar, C, Coscia, F, Mund, A, Hoerning, OB, Bache, N, Apalategui, A, Lubeck, M, Richter, S, Fischer, DS, Raether, O, Park, MA, Meier, F, Theis, FJ & Mann, M 2022, 'Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation', Molecular Systems Biology, vol. 18, no. 3, e10798. https://doi.org/10.15252/msb.202110798

APA

Brunner, A-D., Thielert, M., Vasilopoulou, C., Ammar, C., Coscia, F., Mund, A., Hoerning, O. B., Bache, N., Apalategui, A., Lubeck, M., Richter, S., Fischer, D. S., Raether, O., Park, M. A., Meier, F., Theis, F. J., & Mann, M. (2022). Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation. Molecular Systems Biology, 18(3), [e10798]. https://doi.org/10.15252/msb.202110798

Vancouver

Brunner A-D, Thielert M, Vasilopoulou C, Ammar C, Coscia F, Mund A et al. Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation. Molecular Systems Biology. 2022;18(3). e10798. https://doi.org/10.15252/msb.202110798

Author

Brunner, Andreas-David ; Thielert, Marvin ; Vasilopoulou, Catherine ; Ammar, Constantin ; Coscia, Fabian ; Mund, Andreas ; Hoerning, Ole B ; Bache, Nicolai ; Apalategui, Amalia ; Lubeck, Markus ; Richter, Sabrina ; Fischer, David S ; Raether, Oliver ; Park, Melvin A ; Meier, Florian ; Theis, Fabian J ; Mann, Matthias. / Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation. In: Molecular Systems Biology. 2022 ; Vol. 18, No. 3.

Bibtex

@article{8df9085f3dce47d69ac7d2f8f489d459,
title = "Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation",
abstract = "Single-cell technologies are revolutionizing biology but are today mainly limited to imaging and deep sequencing. However, proteins are the main drivers of cellular function and in-depth characterization of individual cells by mass spectrometry (MS)-based proteomics would thus be highly valuable and complementary. Here, we develop a robust workflow combining miniaturized sample preparation, very low flow-rate chromatography, and a novel trapped ion mobility mass spectrometer, resulting in a more than 10-fold improved sensitivity. We precisely and robustly quantify proteomes and their changes in single, FACS-isolated cells. Arresting cells at defined stages of the cell cycle by drug treatment retrieves expected key regulators. Furthermore, it highlights potential novel ones and allows cell phase prediction. Comparing the variability in more than 430 single-cell proteomes to transcriptome data revealed a stable-core proteome despite perturbation, while the transcriptome appears stochastic. Our technology can readily be applied to ultra-high sensitivity analyses of tissue material, posttranslational modifications, and small molecule studies from small cell counts to gain unprecedented insights into cellular heterogeneity in health and disease.",
author = "Andreas-David Brunner and Marvin Thielert and Catherine Vasilopoulou and Constantin Ammar and Fabian Coscia and Andreas Mund and Hoerning, {Ole B} and Nicolai Bache and Amalia Apalategui and Markus Lubeck and Sabrina Richter and Fischer, {David S} and Oliver Raether and Park, {Melvin A} and Florian Meier and Theis, {Fabian J} and Matthias Mann",
note = "{\textcopyright} 2022 The Authors Published under the terms of the CC BY 4.0 license.",
year = "2022",
doi = "10.15252/msb.202110798",
language = "English",
volume = "18",
journal = "Molecular Systems Biology",
issn = "1744-4292",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation

AU - Brunner, Andreas-David

AU - Thielert, Marvin

AU - Vasilopoulou, Catherine

AU - Ammar, Constantin

AU - Coscia, Fabian

AU - Mund, Andreas

AU - Hoerning, Ole B

AU - Bache, Nicolai

AU - Apalategui, Amalia

AU - Lubeck, Markus

AU - Richter, Sabrina

AU - Fischer, David S

AU - Raether, Oliver

AU - Park, Melvin A

AU - Meier, Florian

AU - Theis, Fabian J

AU - Mann, Matthias

N1 - © 2022 The Authors Published under the terms of the CC BY 4.0 license.

PY - 2022

Y1 - 2022

N2 - Single-cell technologies are revolutionizing biology but are today mainly limited to imaging and deep sequencing. However, proteins are the main drivers of cellular function and in-depth characterization of individual cells by mass spectrometry (MS)-based proteomics would thus be highly valuable and complementary. Here, we develop a robust workflow combining miniaturized sample preparation, very low flow-rate chromatography, and a novel trapped ion mobility mass spectrometer, resulting in a more than 10-fold improved sensitivity. We precisely and robustly quantify proteomes and their changes in single, FACS-isolated cells. Arresting cells at defined stages of the cell cycle by drug treatment retrieves expected key regulators. Furthermore, it highlights potential novel ones and allows cell phase prediction. Comparing the variability in more than 430 single-cell proteomes to transcriptome data revealed a stable-core proteome despite perturbation, while the transcriptome appears stochastic. Our technology can readily be applied to ultra-high sensitivity analyses of tissue material, posttranslational modifications, and small molecule studies from small cell counts to gain unprecedented insights into cellular heterogeneity in health and disease.

AB - Single-cell technologies are revolutionizing biology but are today mainly limited to imaging and deep sequencing. However, proteins are the main drivers of cellular function and in-depth characterization of individual cells by mass spectrometry (MS)-based proteomics would thus be highly valuable and complementary. Here, we develop a robust workflow combining miniaturized sample preparation, very low flow-rate chromatography, and a novel trapped ion mobility mass spectrometer, resulting in a more than 10-fold improved sensitivity. We precisely and robustly quantify proteomes and their changes in single, FACS-isolated cells. Arresting cells at defined stages of the cell cycle by drug treatment retrieves expected key regulators. Furthermore, it highlights potential novel ones and allows cell phase prediction. Comparing the variability in more than 430 single-cell proteomes to transcriptome data revealed a stable-core proteome despite perturbation, while the transcriptome appears stochastic. Our technology can readily be applied to ultra-high sensitivity analyses of tissue material, posttranslational modifications, and small molecule studies from small cell counts to gain unprecedented insights into cellular heterogeneity in health and disease.

U2 - 10.15252/msb.202110798

DO - 10.15252/msb.202110798

M3 - Journal article

C2 - 35226415

VL - 18

JO - Molecular Systems Biology

JF - Molecular Systems Biology

SN - 1744-4292

IS - 3

M1 - e10798

ER -

ID: 303113846