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Influence of node abundance on signaling network state and dynamics analyzed by mass cytometry


Lun, Xiao-Kang; Zanotelli, Vito R T; Wade, James D; Schapiro, Denis; Tognetti, Marco; Dobberstein, Nadine; Bodenmiller, Bernd (2017). Influence of node abundance on signaling network state and dynamics analyzed by mass cytometry. Nature Biotechnology, 35(2):164-172.

Abstract

Signaling networks are key regulators of cellular function. Although the concentrations of signaling proteins are perturbed in disease states, such as cancer, and are modulated by drug therapies, our understanding of how such changes shape the properties of signaling networks is limited. Here we couple mass-cytometry-based single-cell analysis with overexpression of tagged signaling proteins to study the dependence of signaling relationships and dynamics on protein node abundance. Focusing on the epidermal growth factor receptor (EGFR) signaling network in HEK293T cells, we analyze 20 signaling proteins during a 1-h EGF stimulation time course using a panel of 35 antibodies. Data analysis with BP-R2, a measure that quantifies complex signaling relationships, reveals abundance-dependent network states and identifies novel signaling relationships. Further, we show that upstream signaling proteins have abundance-dependent effects on downstream signaling dynamics. Our approach elucidates the influence of node abundance on signal transduction networks and will further our understanding of signaling in health and disease.

Abstract

Signaling networks are key regulators of cellular function. Although the concentrations of signaling proteins are perturbed in disease states, such as cancer, and are modulated by drug therapies, our understanding of how such changes shape the properties of signaling networks is limited. Here we couple mass-cytometry-based single-cell analysis with overexpression of tagged signaling proteins to study the dependence of signaling relationships and dynamics on protein node abundance. Focusing on the epidermal growth factor receptor (EGFR) signaling network in HEK293T cells, we analyze 20 signaling proteins during a 1-h EGF stimulation time course using a panel of 35 antibodies. Data analysis with BP-R2, a measure that quantifies complex signaling relationships, reveals abundance-dependent network states and identifies novel signaling relationships. Further, we show that upstream signaling proteins have abundance-dependent effects on downstream signaling dynamics. Our approach elucidates the influence of node abundance on signal transduction networks and will further our understanding of signaling in health and disease.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Biotechnology
Physical Sciences > Bioengineering
Life Sciences > Applied Microbiology and Biotechnology
Life Sciences > Molecular Medicine
Physical Sciences > Biomedical Engineering
Language:English
Date:1 February 2017
Deposited On:14 Feb 2019 13:03
Last Modified:27 Nov 2020 07:30
Publisher:Nature Publishing Group
ISSN:1087-0156
OA Status:Green
Publisher DOI:https://doi.org/10.1038/nbt.3770

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