Tales of a Fountain of Youth and the invention of medicine illustrate our age-long obsession with two themes: life and death. What it takes to stay alive, and not to be dead, is a basic question in science that is easy to state, and yet difficult to address at a profound level. One striking feature of many living organisms is the ability of individuals to behave in unison by communicating with each other. At life’s microscopic level, living cells can also send and receive chemical signals to communicate with each other in their habitat but for a population of many thousands of cells it remains enigmatic who is communicating with whom, what are the signals, and how the signals work over space and time. We used quantitative experiments and mathematical modelling to systematically explore how mouse Embryonic Stem (ES) cells might cooperate by communicating when differentiating into the first two lineages. We discovered that differentiating mouse ES cells scattered across many centimeters on a dish form one macroscopic entity that either survives or dies in unison if and only if its population-density is above a threshold value. This switch-like behavior is determined by cells that secrete and sense FGF4 that diffuses over many millimeters to activate YAP1-induced survival mechanisms. Our work shows that living cells (in vitro) can rely on macroscopic cooperation to stay alive.

Microorganisms can cooperate with each other, meaning that individual cells work together to pursue a common interest. Cooperation can be crucial for microorganisms to survive stressful environmental conditions. In this work, we report on the cooperative behaviour by the yeast S. cerevisiae and the bacterium E. coli, which stimulates survival and growth at high temperatures. Our lab had already discovered that genetically identical yeast cells cooperate with each other via the secretion of a public good (the antioxidant glutathione), to extend habitability of high temperatures. However, microbes naturally live in communities, where they coexist with other strains and species. These microbial communities are crucial to the health of an ecosystem, but their habitats are warming up due to climate change. So, understanding their response to a rising temperature may be crucial to keep ecosystems healthy. We take it one step further and study the cooperation between different yeast strains at high temperatures. We found that not only a population of genetically identical cells, but also different strains cooperate with each other, to collectively survive under high temperature conditions. We performed so-called co-existence experiments at high temperatures, where we combined two different yeast strains, one genetically fitter than the other. Depending on the initial composition of the mixed population, we obtained two outcomes. In the first outcome, the genetically fitter strain helps the less fit strain to grow. In the second outcome, vice versa, the less fit strain helps the fitter strain to grow. A mathematical model that reproduces the experimental data, predicts an additional outcome, where both strains would help each other to grow. Additionally, we discovered a novel cooperative behaviour at high temperatures in the bacterium E. coli. We found that E. coli cells show similar growth behaviour compared to yeast and we hypothesize that a comparable cooperative behaviour lies at the basis, also regulated by the secretion of a public good. These results suggest that cooperation at high temperatures could be conserved amongst different microbial species.