ArticleMolecular systems biology2018
Cell-specific responses to the cytokine TGFβ are determined by variability in protein levels.
Article in Molecular systems biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- FKBP12 determines ligand-specific SMAD signaling in individual living endothelial cells.iScience · 2026Article
- TGFβ signaling systems are prone to inhibition and ligand competition by coreceptor.bioRxiv : the preprint server for biology · 2026Article
- How memory and adaptation cost shape cell phenotypic dynamics in response to fluctuating environments.bioRxiv : the preprint server for biology · 2025Article
- Integrated mathematical and experimental modeling uncovers enhanced EMT plasticity upon loss of the DLC1 tumor suppressor.PLoS computational biology · 2025Article
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- An integrative phenotype-structured partial differential equation model for the population dynamics of epithelial-mesenchymal transition.NPJ systems biology and applications · 2025Article
- Transcriptional regulators ensuring specific gene expression and decision-making at high TGFβ doses.Life science alliance · 2025Article
- RTF: an R package for modelling time course data.Bioinformatics (Oxford, England) · 2024Article
- Mathematical Modeling and Inference of Epidermal Growth Factor-Induced Mitogen-Activated Protein Kinase Cell Signaling Pathways.International journal of molecular sciences · 2024Review
- Liebig's law of the minimum in the TGF-β/SMAD pathway.PLoS computational biology · 2024Article
- A guide to ERK dynamics, part 1: mechanisms and models.The Biochemical journal · 2023Article
- Impact of HIF1-α/TGF-β/Smad-2/Bax/Bcl2 pathways on cobalt chloride-induced cardiac and hepatorenal dysfunction.Future science OA · 2023Article
- Transcriptional kinetic synergy: A complex landscape revealed by integrating modeling and synthetic biology.Cell systems · 2023Article
- An optimized reporter of the transcription factor hypoxia-inducible factor 1α reveals complex HIF-1α activation dynamics in single cells.The Journal of biological chemistry · 2023Article
- State- and stimulus-specific dynamics of SMAD signaling determine fate decisions in individual cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state.Journal of the Royal Society, Interface · 2023Article
- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Resolving Crosstalk Between Signaling Pathways Using Mathematical Modeling and Time-Resolved Single Cell Data.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Data-based stochastic modeling reveals sources of activity bursts in single-cell TGF-β signaling.PLoS computational biology · 2022Article
- Dynamic Visualization of TGF-β/SMAD3 Transcriptional Responses in Single Living Cells.Cancers · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The cytokine TGFβ provides important information during embryonic development, adult tissue homeostasis, and regeneration. Alterations in the cellular response to TGFβ are involved in severe human diseases. To understand how cells encode the extracellular input and transmit its information to elicit appropriate responses, we acquired quantitative time-resolved measurements of pathway activation at the single-cell level. We established dynamic time warping to quantitatively compare signaling dynamics of thousands of individual cells and described heterogeneous single-cell responses by mathematical modeling. Our combined experimental and theoretical study revealed that the response to a given dose of TGFβ is determined cell specifically by the levels of defined signaling proteins. This heterogeneity in signaling protein expression leads to decomposition of cells into classes with qualitatively distinct signaling dynamics and phenotypic outcome. Negative feedback regulators promote heterogeneous signaling, as a SMAD7 knock-out specifically affected the signal duration in a subpopulation of cells. Taken together, we propose a quantitative framework that allows predicting and testing sources of cellular signaling heterogeneity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.