Model Identifier
BIOMD0000000999
Short description
Model depicting class 2 signaling class observed upon stimulation with 100 pM TGFβ1.
Format
SBML (L2V4)
Related Publication
  • Cell-specific responses to the cytokine TGFb are determined by variability in protein levels. Click here to expand
  • Strasen J, Sarma U, Jentsch M, Bohn S, Sheng C, Horbelt D, Knaus P, Legewie S, Loewer A
  • Molecular systems biology , 1/ 2018 , Volume 14 , Issue 1 , pages: e7733 , PubMed ID: 29371237
  • Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany.
  • The cytokine TGFb provides important information during embryonic development, adult tissue homeostasis, and regeneration. Alterations in the cellular response to TGFb 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 TGFb 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.
Contributors
Submitter of the first revision: Uddipan Sarma
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modellers: Uddipan Sarma, Krishna Kumar Tiwari, Rahuman S Malik-Sheriff

Metadata information

is (2 statements)
BioModels Database BIOMD0000000999
BioModels Database MODEL1712050008

isDescribedBy (1 statement)
PubMed 29371237

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (4 statements)
occursIn (1 statement)
Brenda Tissue Ontology breast epithelial cell

Curation status
Curated
Modelling approach(es)
ordinary differential equation model

Connected external resources