Title: Modeling of Emergent Patterns Within Stem Cell Colonies

Abstract: The differentiation of stem cell colonies into specified tissue types is possible through local and long-distance intercellular communication; however, it is unclear which mechanisms take priority in context-specific situations. Here we consider human induced pluripotent stem cells (hiPSCs) whose therapeutic potential arises from their ability to differentiate into all germ lineages. Prior work in the literature suggests that both cell-autonomous and non-autonomous (e.g. positional) mechanisms determine cell fate during the differentiation of hiSPCs, producing patterns and other system-level features in the process. Informed by experimental data, we develop a collection of agent-based models (ABMs) whose agents (i.e. cells) are each equipped with local rules that govern how the agents interact with their environment and with each other. The purpose of each ABM is to simulate the early differentiation of hiPSCs according to a different set of biological assumptions, with some ABMs using a Boolean network to model potential mechanisms of intercellular communication. We also extend an existing mathematical framework by M. Yereniuk and S.D. Olson which formalizes ABMs to estimate long-term model behavior with respect to time. Our extensions introduce the birth and death of agents into the framework, and our estimates aim to establish connections between local interactions and certain system-level observations. Thus, we study both the emergent behaviors of our ABMs and the dynamics of the local rules governing each agent in order to ascertain which modes of intercellular communication determine cell fate.