New Study Reveals How Cell Competition Helps Human Embryos Thrive and Inspires a Card Game for Future Scientists 

Nature Communications study combines game theory and embryo models to show how competition can underpin cooperation during early human development 

A new study published in Nature Communications has uncovered an unexpected principle of early human development: competition between cells may be essential for cooperation—and ultimately for embryonic success. The study combines evolutionary game theory with human stem cell-derived embryo models to investigate how cell competition contributes to embryo viability. The findings suggest that responsive cellular behaviors, including controlled cell elimination, help regulate embryo size and may represent a fundamental mechanism through which cells cooperate during development. 

Led by a collaborative effort between researchers in Dr. Nika Shakiba’s lab, Dr. Maria Abou Chakra from the University of Toronto and Dr. Mo Ebrahimkhani from the University of Pittsburgh, the study combines evolutionary game theory with advanced human embryo models to explore how individual cells make decisions that shape the development of an embryo. The findings suggest that a process known as cell competition, in which cells eliminate neighboring cells that are less fit, helps ensure healthy development by maintaining the proper size and balance of cells within the embryo. 

While competition is often viewed as a conflict between individuals, the researchers found that it can serve a cooperative role when viewed from the perspective of the developing embryo. 

“We often think of competition and cooperation as opposites,” said Dr. Nika Shakiba. “But our findings suggest that in the earliest stages of human development, competition between cells may actually be what enables cooperation. By responding to the needs of the developing embryo, cells can help ensure the whole system develops successfully.” 

To investigate how cells balance their own survival with the needs of the embryo, the researchers developed a mathematical model known as a collective risk game. In the model, cells can adopt different strategies, including proliferation, inactivity, or eliminating neighboring cells. While killing another cell comes at a cost to the individual cell, the model revealed that this behavior can benefit the group when the embryo exceeds its target size and its chances of survival are reduced. 

The researchers then tested these predictions using laboratory-grown human embryo models known as heX-embryoids. They found that successful embryoids formed within a size range that closely resembles the native human embryonic disc. When cell death was experimentally inhibited, the embryoids became larger and developed defects, supporting the prediction that controlled cell elimination plays an important role in maintaining healthy development. 

The findings suggest that cells adopt responsive strategies during the earliest stages of development, adjusting their behavior according to the needs of the embryo. Rather than acting solely in their own interest, cells can engage in behaviors that support the success of the larger collective. The study therefore points to a surprising conclusion: competition among cells may be a key mechanism through which cooperation emerges during embryonic development. 

From Research Paper to Card Game 

The impact of the project has extended well beyond the laboratory. 

Inspired by the game’s underlying concepts, members of the Shakiba lab, Joshua de Guzman and Rafael Alkalai, created a card game that translates the science into an engaging educational experience for students and aspiring scientists. The game has been featured at numerous outreach events, allowing participants to explore how cooperation, competition, and decision-making influence biological systems. 

Players take on the role of cells within a developing embryo, making strategic choices while balancing individual success with the needs of the group—the same challenge explored in the research itself. 

By transforming a sophisticated scientific model into a hands-on learning tool, the team hopes to make developmental biology more accessible while inspiring the next generation of researchers. 

The study demonstrates that competition and cooperation are not opposing forces. Instead, in the earliest stages of life, they may work together to help ensure healthy development, offering new insights into one of biology’s most fundamental questions: how individual cells come together to build a successful organism. 

Read the paper here.