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bioRxiv · 10.1101/2020.12.20.423651

Global community effect: large-scale cooperation yields collective survival of differentiating embryonic stem cells

Daneshpour, H.·van den Bersselaar, P.·Youk, H.
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Abstract

Cells can help each other replicate by communicating with diffusible molecules. In cell cultures, molecules may diffuse within a cell colony or between adjacent or distant colonies. Determining which cell helps which cells replication is challenging. We developed a systematic approach, integrating modeling and experiments, for determining the length-scales of cell-cell communication (from microns to centimeters). With this approach, we discovered that differentiating murine ES cells, scattered across centimeters on a dish, communicate over millimeters to form one macroscopic entity that survives if and only if its centimeter-scale population-density is above a threshold value. Single-cell-level measurements, transcriptomics, and modeling revealed that this "macroscopic quorum sensing" arises from differentiating ES cells secreting and sensing survival-promoting FGF4 that diffuses over millimeters and activates YAP1-induced survival mechanisms. Through the same mechanism, a lone macroscopic, but not microscopic, colony survives differentiation. Our work rigorously establishes that in vitro ES-cell differentiation relies on macroscopic cooperation.

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Daneshpour, H., van den Bersselaar, P., Youk, H.. 2020-12-21. Global community effect: large-scale cooperation yields collective survival of differentiating embryonic stem cells. https://doi.org/10.1101/2020.12.20.423651

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