Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells

Autores
Raina, Dhruv; Fabris, Fiorella; Morelli, Luis Guillermo; Schroter, Christian
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Signal transduction networks generate characteristic dynamic activities to process extracellular signals and guide cell fate decisions such as to divide or differentiate. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, only a few studies have addressed the dynamic activity of the FGF/ERK signaling network in pluripotent cells at high time resolution. Here, we use live cell sensors in wild-type and Fgf4-mutant mouse embryonic stem cells to measure dynamic ERK activity in single cells, for defined ligand concentrations and differentiation states. These sensors reveal pulses of ERK activity. Pulsing patterns are heterogeneous between individual cells. Consecutive pulse sequences occur more frequently than expected from simple stochastic models. Sequences become more prevalent with higher ligand concentration, but are rarer in more differentiated cells. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells. The resulting heterogeneous dynamic signaling activities add a new dimension to cellular heterogeneity that may be linked to divergent fate decisions in stem cell cultures.
Fil: Raina, Dhruv. Institut Max Planck fur Molekulare Physiologie; Alemania
Fil: Fabris, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Morelli, Luis Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Institut Max Planck fur Molekulare Physiologie; Alemania
Fil: Schroter, Christian. Institut Max Planck fur Molekulare Physiologie; Alemania
Materia
CELL CYCLE
FGF/ERK SIGNALING
MOUSE EMBRYONIC STEM CELLS
OSCILLATIONS
SIGNAL TRANSDUCTION NETWORKS
TIME SERIES ANALYSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/214294
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/214294
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cellsRaina, DhruvFabris, FiorellaMorelli, Luis GuillermoSchroter, ChristianCELL CYCLEFGF/ERK SIGNALINGMOUSE EMBRYONIC STEM CELLSOSCILLATIONSSIGNAL TRANSDUCTION NETWORKSTIME SERIES ANALYSIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1Signal transduction networks generate characteristic dynamic activities to process extracellular signals and guide cell fate decisions such as to divide or differentiate. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, only a few studies have addressed the dynamic activity of the FGF/ERK signaling network in pluripotent cells at high time resolution. Here, we use live cell sensors in wild-type and Fgf4-mutant mouse embryonic stem cells to measure dynamic ERK activity in single cells, for defined ligand concentrations and differentiation states. These sensors reveal pulses of ERK activity. Pulsing patterns are heterogeneous between individual cells. Consecutive pulse sequences occur more frequently than expected from simple stochastic models. Sequences become more prevalent with higher ligand concentration, but are rarer in more differentiated cells. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells. The resulting heterogeneous dynamic signaling activities add a new dimension to cellular heterogeneity that may be linked to divergent fate decisions in stem cell cultures.Fil: Raina, Dhruv. Institut Max Planck fur Molekulare Physiologie; AlemaniaFil: Fabris, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Morelli, Luis Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Institut Max Planck fur Molekulare Physiologie; AlemaniaFil: Schroter, Christian. Institut Max Planck fur Molekulare Physiologie; AlemaniaCompany of Biologists2022-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/214294Raina, Dhruv; Fabris, Fiorella; Morelli, Luis Guillermo; Schroter, Christian; Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells; Company of Biologists; Development; 149; 4; 2-2022; 1-390950-1991CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1242/dev.199710info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:19:34Zoai:ri.conicet.gov.ar:11336/214294instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:19:35.23CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
title Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
spellingShingle Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
Raina, Dhruv
CELL CYCLE
FGF/ERK SIGNALING
MOUSE EMBRYONIC STEM CELLS
OSCILLATIONS
SIGNAL TRANSDUCTION NETWORKS
TIME SERIES ANALYSIS
title_short Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
title_full Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
title_fullStr Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
title_full_unstemmed Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
title_sort Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
dc.creator.none.fl_str_mv Raina, Dhruv
Fabris, Fiorella
Morelli, Luis Guillermo
Schroter, Christian
author Raina, Dhruv
author_facet Raina, Dhruv
Fabris, Fiorella
Morelli, Luis Guillermo
Schroter, Christian
author_role author
author2 Fabris, Fiorella
Morelli, Luis Guillermo
Schroter, Christian
author2_role author
author
author
dc.subject.none.fl_str_mv CELL CYCLE
FGF/ERK SIGNALING
MOUSE EMBRYONIC STEM CELLS
OSCILLATIONS
SIGNAL TRANSDUCTION NETWORKS
TIME SERIES ANALYSIS
topic CELL CYCLE
FGF/ERK SIGNALING
MOUSE EMBRYONIC STEM CELLS
OSCILLATIONS
SIGNAL TRANSDUCTION NETWORKS
TIME SERIES ANALYSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Signal transduction networks generate characteristic dynamic activities to process extracellular signals and guide cell fate decisions such as to divide or differentiate. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, only a few studies have addressed the dynamic activity of the FGF/ERK signaling network in pluripotent cells at high time resolution. Here, we use live cell sensors in wild-type and Fgf4-mutant mouse embryonic stem cells to measure dynamic ERK activity in single cells, for defined ligand concentrations and differentiation states. These sensors reveal pulses of ERK activity. Pulsing patterns are heterogeneous between individual cells. Consecutive pulse sequences occur more frequently than expected from simple stochastic models. Sequences become more prevalent with higher ligand concentration, but are rarer in more differentiated cells. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells. The resulting heterogeneous dynamic signaling activities add a new dimension to cellular heterogeneity that may be linked to divergent fate decisions in stem cell cultures.
Fil: Raina, Dhruv. Institut Max Planck fur Molekulare Physiologie; Alemania
Fil: Fabris, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Morelli, Luis Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Institut Max Planck fur Molekulare Physiologie; Alemania
Fil: Schroter, Christian. Institut Max Planck fur Molekulare Physiologie; Alemania
description Signal transduction networks generate characteristic dynamic activities to process extracellular signals and guide cell fate decisions such as to divide or differentiate. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, only a few studies have addressed the dynamic activity of the FGF/ERK signaling network in pluripotent cells at high time resolution. Here, we use live cell sensors in wild-type and Fgf4-mutant mouse embryonic stem cells to measure dynamic ERK activity in single cells, for defined ligand concentrations and differentiation states. These sensors reveal pulses of ERK activity. Pulsing patterns are heterogeneous between individual cells. Consecutive pulse sequences occur more frequently than expected from simple stochastic models. Sequences become more prevalent with higher ligand concentration, but are rarer in more differentiated cells. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells. The resulting heterogeneous dynamic signaling activities add a new dimension to cellular heterogeneity that may be linked to divergent fate decisions in stem cell cultures.
publishDate 2022
dc.date.none.fl_str_mv 2022-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/214294
Raina, Dhruv; Fabris, Fiorella; Morelli, Luis Guillermo; Schroter, Christian; Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells; Company of Biologists; Development; 149; 4; 2-2022; 1-39
0950-1991
CONICET Digital
CONICET
url http://hdl.handle.net/11336/214294
identifier_str_mv Raina, Dhruv; Fabris, Fiorella; Morelli, Luis Guillermo; Schroter, Christian; Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells; Company of Biologists; Development; 149; 4; 2-2022; 1-39
0950-1991
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1242/dev.199710
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846083344830300160
score 13.22299

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