A multi-scale approach reveals that NF-kappa B cRel enforces a B-cell decision to divide

作者：Shokhirev Maxim N; Almaden Jonathan; Davis Turak Jeremy; Birnbaum Harry A; Russell Theresa M; Vargas Jesse A D; Hoffmann Alexander^*

来源：Molecular Systems Biology, 2015, 11(2): 783-783.

DOI：10.15252/msb.20145554

• apoptosis
• B-lymphocyte
• cell cycle
• cell fate decision
• NF-kappa B cRel

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-kappa B signaling, the cell cycle, and apoptosis. Combining modeling and experimentation, we found that NF-kappa B 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.

• 出版日期2015-2