Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling
Abstract Stimulation of PC‐12 cells with epidermal (EGF) versus nerve (NGF) growth factors (GFs) biases the distribution between transient and sustained single‐cell ERK activity states, and between proliferation and differentiation fates within a cell population. We report that fibroblast GF (FGF2)...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2019-11-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20198947 |
| _version_ | 1797282097750081536 |
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| author | Yannick Blum Jan Mikelson Maciej Dobrzyński Hyunryul Ryu Marc‐Antoine Jacques Noo Li Jeon Mustafa Khammash Olivier Pertz |
| author_facet | Yannick Blum Jan Mikelson Maciej Dobrzyński Hyunryul Ryu Marc‐Antoine Jacques Noo Li Jeon Mustafa Khammash Olivier Pertz |
| author_sort | Yannick Blum |
| collection | DOAJ |
| description | Abstract Stimulation of PC‐12 cells with epidermal (EGF) versus nerve (NGF) growth factors (GFs) biases the distribution between transient and sustained single‐cell ERK activity states, and between proliferation and differentiation fates within a cell population. We report that fibroblast GF (FGF2) evokes a distinct behavior that consists of a gradually changing population distribution of transient/sustained ERK signaling states in response to increasing inputs in a dose response. Temporally controlled GF perturbations of MAPK signaling dynamics applied using microfluidics reveal that this wider mix of ERK states emerges through the combination of an intracellular feedback, and competition of FGF2 binding to FGF receptors (FGFRs) and heparan sulfate proteoglycan (HSPG) co‐receptors. We show that the latter experimental modality is instructive for model selection using a Bayesian parameter inference. Our results provide novel insights into how different receptor tyrosine kinase (RTK) systems differentially wire the MAPK network to fine‐tune fate decisions at the cell population level. |
| first_indexed | 2024-03-07T17:08:00Z |
| format | Article |
| id | doaj.art-9c66613fe22d4e1086054aeeee741976 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:08:00Z |
| publishDate | 2019-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-9c66613fe22d4e1086054aeeee7419762024-03-03T02:25:38ZengSpringer NatureMolecular Systems Biology1744-42922019-11-011511n/an/a10.15252/msb.20198947Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signalingYannick Blum0Jan Mikelson1Maciej Dobrzyński2Hyunryul Ryu3Marc‐Antoine Jacques4Noo Li Jeon5Mustafa Khammash6Olivier Pertz7Institute of Cell Biology University of Bern Bern SwitzerlandDepartment of Biosystems Science and Engineering ETH Zurich Basel SwitzerlandInstitute of Cell Biology University of Bern Bern SwitzerlandInstitute of Advanced Machinery and Design Seoul National University Seoul KoreaInstitute of Cell Biology University of Bern Bern SwitzerlandInstitute of Advanced Machinery and Design Seoul National University Seoul KoreaDepartment of Biosystems Science and Engineering ETH Zurich Basel SwitzerlandInstitute of Cell Biology University of Bern Bern SwitzerlandAbstract Stimulation of PC‐12 cells with epidermal (EGF) versus nerve (NGF) growth factors (GFs) biases the distribution between transient and sustained single‐cell ERK activity states, and between proliferation and differentiation fates within a cell population. We report that fibroblast GF (FGF2) evokes a distinct behavior that consists of a gradually changing population distribution of transient/sustained ERK signaling states in response to increasing inputs in a dose response. Temporally controlled GF perturbations of MAPK signaling dynamics applied using microfluidics reveal that this wider mix of ERK states emerges through the combination of an intracellular feedback, and competition of FGF2 binding to FGF receptors (FGFRs) and heparan sulfate proteoglycan (HSPG) co‐receptors. We show that the latter experimental modality is instructive for model selection using a Bayesian parameter inference. Our results provide novel insights into how different receptor tyrosine kinase (RTK) systems differentially wire the MAPK network to fine‐tune fate decisions at the cell population level.https://doi.org/10.15252/msb.20198947cell fate determinationERK signaling dynamicsmechanistic modelingmicrofluidicsparameter estimation |
| spellingShingle | Yannick Blum Jan Mikelson Maciej Dobrzyński Hyunryul Ryu Marc‐Antoine Jacques Noo Li Jeon Mustafa Khammash Olivier Pertz Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling Molecular Systems Biology cell fate determination ERK signaling dynamics mechanistic modeling microfluidics parameter estimation |
| title | Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling |
| title_full | Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling |
| title_fullStr | Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling |
| title_full_unstemmed | Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling |
| title_short | Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling |
| title_sort | temporal perturbation of erk dynamics reveals network architecture of fgf2 mapk signaling |
| topic | cell fate determination ERK signaling dynamics mechanistic modeling microfluidics parameter estimation |
| url | https://doi.org/10.15252/msb.20198947 |
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