Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells
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Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells. / Adlung, Lorenz; Stapor, Paul; Tönsing, Christian; Schmiester, Leonard; Schwarzmüller, Luisa E.; Postawa, Lena; Wang, Dantong; Timmer, Jens; Klingmüller, Ursula; Hasenauer, Jan; Schilling, Marcel.
In: CELL REP, Vol. 36, No. 6, 109507, 10.08.2021, p. 109507.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells
AU - Adlung, Lorenz
AU - Stapor, Paul
AU - Tönsing, Christian
AU - Schmiester, Leonard
AU - Schwarzmüller, Luisa E.
AU - Postawa, Lena
AU - Wang, Dantong
AU - Timmer, Jens
AU - Klingmüller, Ursula
AU - Hasenauer, Jan
AU - Schilling, Marcel
PY - 2021/8/10
Y1 - 2021/8/10
N2 - 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.
AB - 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.
UR - https://doi.org/10.1016/j.celrep.2021.109507
U2 - 10.1016/j.celrep.2021.109507
DO - 10.1016/j.celrep.2021.109507
M3 - SCORING: Journal article
C2 - 34380040
VL - 36
SP - 109507
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 6
M1 - 109507
ER -