PuSH - Publication Server of Helmholtz Zentrum München: Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Adlung, L.* ; Stapor, P. ; Tönsing, C.* ; Schmiester, L. ; Schwarzmüller, L.E.* ; Postawa, L.* ; Wang, D. ; Timmer, J.* ; Klingmüller, U.* ; Hasenauer, J. ; Schilling, M.*

Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells.

Cell Rep. 36:109507 (2021)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

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.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Apoptosis ; Cell Fate Decision ; Cfu-e Cells ; Epo ; Heterogeneity ; Jak/stat ; Mathematical Modeling ; Signal Transduction ; Single-cell Modeling ; Transcription Factor; Parameter-estimation; Stat5a(-/-)5b(-/-) Mice; Tyrosine Residues; Gene-expression; Flow-cytometry; Dna-binding; Erythropoietin; Identification; Stat5; Phosphorylation

ISSN (print) / ISBN 2211-1247

e-ISSN 2211-1247

Journal Cell Reports

Quellenangaben Volume: 36, Issue: 6, Article Number: 109507

Publisher Cell Press

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants Deutsche Forschungsgemeinschaft (DFG)
European Union's Horizon 2020 research and innovation program (CanPathPro)
German Ministry of Education and Research (BMBF) within the e:Bio collaborative research projects ''Systems Biology of Erythropoietin'' (SBEpo)
German Federal Ministry of Education and Research (BMBF)
Systems Medicine network LiSyM
Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy
state of Baden-Wurttemberg, Germany, through bwHPC