Model Identifier
BIOMD0000001077
Short description

A mathematical model for cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells
Format
SBML (L2V4)
Related Publication
  • Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells. Click here to expand
  • Lorenz Adlung, Paul Stapor, Christian Tönsing, Leonard Schmiester, Luisa E Schwarzmüller, Lena Postawa, Dantong Wang, Jens Timmer, Ursula Klingmüller, J Hasenauer, Marcel Schilling
  • Cell reports , 8/ 2021 , Volume 36 , Issue 6 , pages: 109507 , PubMed ID: 34380040
  • Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Survival or apoptosis is a binary decision in individual cells. However, at the cell-population level, a graded increase in survival of colony-forming unit-erythroid (CFU-E) cells is observed upon stimulation with erythropoietin (Epo). To identify components of Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5) signal transduction that contribute to the graded population response, we extended a cell-population-level model calibrated with experimental data to study the behavior in single cells. The single-cell model shows that the high cell-to-cell variability in nuclear phosphorylated STAT5 is caused by variability in the amount of Epo receptor (EpoR):JAK2 complexes and of SHP1, as well as the extent of nuclear import because of the large variance in the cytoplasmic volume of CFU-E cells. 24-118 pSTAT5 molecules in the nucleus for 120 min are sufficient to ensure cell survival. Thus, variability in membrane-associated processes is sufficient to convert a switch-like behavior at the single-cell level to a graded population-level response.
Contributors
Submitter of the first revision: Marcel Schilling
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modellers: Marcel Schilling, Krishna Kumar Tiwari

Metadata information

is (2 statements)
BioModels Database BIOMD0000001077
BioModels Database MODEL2103080001

isDescribedBy (2 statements)
PubMed 34380040
PubMed 34380040

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (3 statements)
unknownQualifier (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

occursIn (1 statement)
Brenda Tissue Ontology erythroid progenitor cell

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

Connected external resources