Investigating Motility and Pattern Formation in Pluripotent Stem Cells Through AgentBased Modeling Understanding and predicting the pattern formation in groups of pluripotent stem cells has the potential to improve efficiency and efficacy of stem cell therapies. However, the underlying molecular mechanisms of pluripotent stem cell behaviors are highly complex and are currently still not fully understood. A key practical question is whether deep biological modelling of the cells is essential to predict their pattern formation, or whether there is sufficient predictive power in simply modelling their behaviors and interactions at a higher level. This study focuses on the social interactions and behaviors of pluripotent stem cells at a highlevel to predict aggregate crowd behaviors within a level of uncertainty. Agentbased modelling was applied to study the pattern formation in pluripotent stem cells. Five models were established to test four biologically plausible rules of cell motility in terms of: a) velocity, b) directional persistence time, c) directional movements, and d) border effect. We found that it is possible that cellsu0027 directional movements based on local density play an important role of the pattern formation, and pattern formation in pluripotent stem cells is governed by a complex combination of rules in our agentbased model simulations, which account for much of the variability observed in experimental findings.

Disentangling a complex response in cell reprogramming and probing the Waddington landscape by automatic construction of Petri nets. Abstract   We analyzed the developmental switch to sporulation of a multinucleate Physarum polycephalum plasmodial cell, a complex response to phytochrome photoreceptor activation. Automatic construction of Petri nets representing finite state machines assembled from trajectories of differential gene expression in single cells revealed alternative, genotypedependent interconnected developmental routes and identified reversible steps, metastable states, commitment points, and subsequent irreversible steps together with molecular signatures associated with cell fate decision and differentiation. Formation of cyclic transits identified by transition invariants in mutants that are locked in a proliferative state is remarkable considering the view that oncogenic alterations may cause the formation of cancer attractors. We conclude that the Petri net approach is useful to probe the Waddington landscape of cellular reprogramming, to disentangle developmental routes for the reconstruction of the gene regulatory network, and to understand how genetic alterations or physiological conditions reshape the landscape eventually creating new basins of attraction. Unraveling the complexity of pathogenesis, disease progression, drug response or the analysis of attractor landscapes in other complex systems of uncertain structure might be additional fields of application.