A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divide
Abstract Understanding the functions of multi‐cellular organs in terms of the molecular networks within each cell is an important step in the quest to predict phenotype from genotype. B‐lymphocyte population dynamics, which are predictive of immune response and vaccine effectiveness, are determined...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-02-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20145554 |
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| _version_ | 1849235723430920192 |
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| author | Maxim N Shokhirev Jonathan Almaden Jeremy Davis‐Turak Harry A Birnbaum Theresa M Russell Jesse A D Vargas Alexander Hoffmann |
| author_facet | Maxim N Shokhirev Jonathan Almaden Jeremy Davis‐Turak Harry A Birnbaum Theresa M Russell Jesse A D Vargas Alexander Hoffmann |
| author_sort | Maxim N Shokhirev |
| collection | DOAJ |
| description | Abstract Understanding the functions of multi‐cellular organs in terms of the molecular networks within each cell is an important step in the quest to predict phenotype from genotype. B‐lymphocyte population dynamics, which are predictive of immune response and vaccine effectiveness, are determined by individual cells undergoing division or death seemingly stochastically. Based on tracking single‐cell time‐lapse trajectories of hundreds of B cells, single‐cell transcriptome, and immunofluorescence analyses, we constructed an agent‐based multi‐modular computational model to simulate lymphocyte population dynamics in terms of the molecular networks that control NF‐κB signaling, the cell cycle, and apoptosis. Combining modeling and experimentation, we found that NF‐κB cRel enforces the execution of a cellular decision between mutually exclusive fates by promoting survival in growing cells. But as cRel deficiency causes growing B cells to die at similar rates to non‐growing cells, our analysis reveals that the phenomenological decision model of wild‐type cells is rooted in a biased race of cell fates. We show that a multi‐scale modeling approach allows for the prediction of dynamic organ‐level physiology in terms of intra‐cellular molecular networks. |
| format | Article |
| id | doaj-art-cec928a1a4fe4d4abbe89e013f33ebc9 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2015-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-cec928a1a4fe4d4abbe89e013f33ebc92025-08-20T04:02:41ZengSpringer NatureMolecular Systems Biology1744-42922015-02-0111211610.15252/msb.20145554A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divideMaxim N Shokhirev0Jonathan Almaden1Jeremy Davis‐Turak2Harry A Birnbaum3Theresa M Russell4Jesse A D Vargas5Alexander Hoffmann6Department of Chemistry and Biochemistry, Signaling Systems Laboratory, UCSDDepartment of Chemistry and Biochemistry, Signaling Systems Laboratory, UCSDDepartment of Chemistry and Biochemistry, Signaling Systems Laboratory, UCSDDepartment of Chemistry and Biochemistry, Signaling Systems Laboratory, UCSDFluidigm CorporationDepartment of Chemistry and Biochemistry, Signaling Systems Laboratory, UCSDDepartment of Chemistry and Biochemistry, Signaling Systems Laboratory, UCSDAbstract Understanding the functions of multi‐cellular organs in terms of the molecular networks within each cell is an important step in the quest to predict phenotype from genotype. B‐lymphocyte population dynamics, which are predictive of immune response and vaccine effectiveness, are determined by individual cells undergoing division or death seemingly stochastically. Based on tracking single‐cell time‐lapse trajectories of hundreds of B cells, single‐cell transcriptome, and immunofluorescence analyses, we constructed an agent‐based multi‐modular computational model to simulate lymphocyte population dynamics in terms of the molecular networks that control NF‐κB signaling, the cell cycle, and apoptosis. Combining modeling and experimentation, we found that NF‐κB cRel enforces the execution of a cellular decision between mutually exclusive fates by promoting survival in growing cells. But as cRel deficiency causes growing B cells to die at similar rates to non‐growing cells, our analysis reveals that the phenomenological decision model of wild‐type cells is rooted in a biased race of cell fates. We show that a multi‐scale modeling approach allows for the prediction of dynamic organ‐level physiology in terms of intra‐cellular molecular networks.https://doi.org/10.15252/msb.20145554apoptosisB‐lymphocytecell cyclecell fate decisionNF‐κB cRel |
| spellingShingle | Maxim N Shokhirev Jonathan Almaden Jeremy Davis‐Turak Harry A Birnbaum Theresa M Russell Jesse A D Vargas Alexander Hoffmann A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divide Molecular Systems Biology apoptosis B‐lymphocyte cell cycle cell fate decision NF‐κB cRel |
| title | A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divide |
| title_full | A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divide |
| title_fullStr | A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divide |
| title_full_unstemmed | A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divide |
| title_short | A multi‐scale approach reveals that NF‐κB cRel enforces a B‐cell decision to divide |
| title_sort | multi scale approach reveals that nf κb crel enforces a b cell decision to divide |
| topic | apoptosis B‐lymphocyte cell cycle cell fate decision NF‐κB cRel |
| url | https://doi.org/10.15252/msb.20145554 |
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