Laura F. Strube, Adam L. MacLean
Cells make fate decisions and phenotypic changes throughout life. Particularly prominent are their roles in development, immune responses, and cancer progression. In each case, the outcome of a decision depends on a complex interplay between signal transduction pathways within cells and feedbacks to and from the surrounding microenvironment. Some cell state transitions might follow “simple” trajectories, e.g. between binary fates, but increasingly, evidence points towards wider spectra of accessible cell states under complex cell- and environment-dependent control. Additionally, transcriptional states are not always sufficient to describe these states: post-transcriptional regulation via epigenetic modifications, microRNAs, etc. also play important roles in determining cell fate. Thus, understanding and predicting how tissue microenvironmental signals impact cell phenotypes demand a systems-level perspective that integrates mathematical modeling with quantitative tools. This minisymposium highlights the state-of-the-art in this domain: coupling quantitative experimental and computational methods to reveal the molecular underpinnings of cell fate decision-making phenomena. The talks comprising this session will describe discoveries in model systems ranging from pro- vs. anti-inflammatory responses in macrophages and the epithelial-to-mesenchymal transition in development, to the multiscale effects of microenvironmental signaling on cell fate decisions in the developing mammary gland. Innovative approaches these works employ include multiscale modeling, genomics analyses, and new methods for machine learning coupled with differential equation modeling. Overall, these talks will reveal new understanding into dynamic cell phenotypes through quantitative modeling across biological scales.