ArticleProceedings of the National Academy of Sciences of the United States of America2014
Single-cell mass cytometry of TCR signaling: amplification of small initial differences results in low ERK activation in NOD mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- APOE4 Drives Uniquely Dysfunctional Human Microglial States in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Signal amplification by cyclic extension enables high-sensitivity single-cell mass cytometry.Nature biotechnology · 2025Article
- Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.ACS nano · 2024Article
- Single-cell mass cytometry in immunological skin diseases.Frontiers in immunology · 2024Review
- Article
- Albumin nanoparticle containing a PI3Kγ inhibitor and paclitaxel in combination with α-PD1 induces tumor remission of breast cancer in mice.Science translational medicine · 2022Article
- Differential Kinase Activity Across Prostate Tumor Compartments Defines Sensitivity to Target Inhibition.Cancer research · 2022Article
- Towards high throughput and high information coverage: advanced single-cell mass spectrometric techniques.Analytical and bioanalytical chemistry · 2022Review
- Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8Immunity · 2021Article
- Single-cell proteomic analysis.WIREs mechanisms of disease · 2021Review
- The use and limitations of single-cell mass cytometry for studying human microglia function.Brain pathology (Zurich, Switzerland) · 2020Review
- High-Dimensional Data Analysis Algorithms Yield Comparable Results for Mass Cytometry and Spectral Flow Cytometry Data.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2020Article
- Article
- Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions.The Journal of clinical investigation · 2019Article
- Understanding the Dynamics of T-Cell Activation in Health and Disease Through the Lens of Computational Modeling.JCO clinical cancer informatics · 2019Review
- A Microfluidic Fluorescent Flow Cytometry Capable of Quantifying Cell Sizes and Numbers of Specific Cytosolic Proteins.Scientific reports · 2018Article
- Advancing systems immunology through data-driven statistical analysis.Current opinion in biotechnology · 2018Review
- Absolute Copy Numbers of β-Actin Proteins Collected from 10,000 Single Cells.Micromachines · 2018Article
- Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort.Journal of autoimmunity · 2018Article
- Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cells.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Signaling from the T-cell receptor (TCR) conditions T-cell differentiation and activation, requiring exquisite sensitivity and discrimination. Using mass cytometry, a high-dimensional technique that can probe multiple signaling nodes at the single-cell level, we interrogate TCR signaling dynamics in control C57BL/6 and autoimmunity-prone nonobese diabetic (NOD) mice, which show ineffective ERK activation after TCR triggering. By quantitating signals at multiple steps along the signaling cascade and parsing the phosphorylation level of each node as a function of its predecessors, we show that a small impairment in initial pCD3ζ activation resonates farther down the signaling cascade and results in larger defects in activation of the ERK1/2-S6 and IκBα modules. This nonlinear property of TCR signaling networks, which magnifies small initial differences during signal propagation, also applies in cells from B6 mice activated at different levels of intensity. Impairment in pCD3ζ and pSLP76 is not a feedback consequence of a primary deficiency in ERK activation because no proximal signaling defect was observed in Erk2 KO T cells. These defects, which were manifest at all stages of T-cell differentiation from early thymic pre-T cells to memory T cells, may condition the imbalanced immunoregulation and tolerance in NOD T cells. More generally, this amplification of small initial differences in signal intensity may explain how T cells discriminate between closely related ligands and adopt strongly delineated cell fates.
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