Investigating Motility and Pattern Formation in Pluripotent Stem Cells Through Agent-Based 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 high-level to predict aggregate crowd behaviors within a level of uncertainty. Agent-based 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 cells' 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 agent-based model simulations, which account for much of the variability observed in experimental findings.

[1]  Marco A. Janssen An Introduction to agent-based modeling. , 2018 .

[2]  A. Martinez Arias,et al.  Brachyury cooperates with Wnt/β-catenin signalling to elicit primitive-streak-like behaviour in differentiating mouse embryonic stem cells , 2014, BMC Biology.

[3]  Dirk P. Kroese,et al.  Kernel density estimation via diffusion , 2010, 1011.2602.

[4]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[5]  Nathan O. Loewke,et al.  Dynamic and social behaviors of human pluripotent stem cells , 2015, Scientific Reports.

[6]  Minhong Wang,et al.  Agent-Based Modelling of Pattern Formation in Pluripotent Stem Cells: Initial Experiments and Results , 2018, 2018 11th International Congress on Image and Signal Processing, BioMedical Engineering and Informatics (CISP-BMEI).

[7]  M. Bissell,et al.  Self-organization of engineered epithelial tubules by differential cellular motility , 2009, Proceedings of the National Academy of Sciences.

[8]  F. Guilak,et al.  Control of stem cell fate by physical interactions with the extracellular matrix. , 2009, Cell stem cell.

[9]  K. Freude,et al.  Systems Biology and Stem Cell Pluripotency: Revisiting the Discovery of Induced Pluripotent Stem Cell , 2016 .

[10]  William Rand,et al.  An Introduction to Agent-Based Modeling: Modeling Natural, Social, and Engineered Complex Systems with NetLogo , 2015 .

[11]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[12]  P. Bonaldo,et al.  Extracellular matrix: A dynamic microenvironment for stem cell niche , 2014, Biochimica et biophysica acta.

[13]  G. Blin,et al.  Distinct Wnt-driven primitive streak-like populations reflect in vivo lineage precursors , 2015, Development.

[14]  O. Troyanskaya,et al.  Geometrical confinement controls the asymmetric patterning of brachyury in cultures of pluripotent cells , 2018, Development.

[15]  A. M. Arias,et al.  Brachyury cooperates with Wnt/β-Catenin signalling to elicit Primitive Streak like behaviour in differentiating mouse ES cells , 2014, bioRxiv.