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

Standard

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, Jahrgang 36, Nr. 6, 109507, 10.08.2021, S. 109507.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Adlung, L, Stapor, P, Tönsing, C, Schmiester, L, Schwarzmüller, LE, Postawa, L, Wang, D, Timmer, J, Klingmüller, U, Hasenauer, J & Schilling, M 2021, 'Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells', CELL REP, Jg. 36, Nr. 6, 109507, S. 109507. https://doi.org/10.1016/j.celrep.2021.109507

APA

Adlung, L., Stapor, P., Tönsing, C., Schmiester, L., Schwarzmüller, L. E., Postawa, L., Wang, D., Timmer, J., Klingmüller, U., Hasenauer, J., & Schilling, M. (2021). Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells. CELL REP, 36(6), 109507. [109507]. https://doi.org/10.1016/j.celrep.2021.109507

Vancouver

Bibtex

@article{49c4bcf79c21467195c12b066e0bb88b,
title = "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.",
author = "Lorenz Adlung and Paul Stapor and Christian T{\"o}nsing and Leonard Schmiester and Schwarzm{\"u}ller, {Luisa E.} and Lena Postawa and Dantong Wang and Jens Timmer and Ursula Klingm{\"u}ller and Jan Hasenauer and Marcel Schilling",
year = "2021",
month = aug,
day = "10",
doi = "10.1016/j.celrep.2021.109507",
language = "English",
volume = "36",
pages = "109507",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

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 -