Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells
Abstract: 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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Cell reports. - 36, 6 (2021) , 109507, ISSN: 2211-1247
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
-
Universität
- (when)
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2024
- Creator
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Adlung, Lorenz
Stapor, Paul
Tönsing, Christian
Schmiester, Leonard
Schwarzmüller, Luisa E.
Postawa, Lena
Wang, Dantong
Timmer, Jens
Klingmüller, Ursula
Hasenauer, Jan
Schilling, Marcel
- DOI
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10.1016/j.celrep.2021.109507
- URN
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urn:nbn:de:bsz:25-freidok-2479485
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 11:00 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Adlung, Lorenz
- Stapor, Paul
- Tönsing, Christian
- Schmiester, Leonard
- Schwarzmüller, Luisa E.
- Postawa, Lena
- Wang, Dantong
- Timmer, Jens
- Klingmüller, Ursula
- Hasenauer, Jan
- Schilling, Marcel
- Universität
Time of origin
- 2024
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