Macroscopic quorum sensing sustains differentiating embryonic stem cells
Hirad Daneshpour (TU Delft - Applied Sciences, University of Massachusetts Medical School, Kavli institute of nanoscience Delft)
Pim van den Bersselaar (TU Delft - OLD BN/Hyun Youk Lab, Kavli institute of nanoscience Delft, University of Massachusetts Medical School)
Chun Hao Chao (University of Massachusetts Medical School)
Thomas G. Fazzio (University of Massachusetts Medical School)
Hyun Youk (CIFAR, University of Massachusetts Medical School)
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Abstract
Cells can secrete molecules that help each other’s replication. In cell cultures, chemical signals might diffuse only within a cell colony or between colonies. A chemical signal’s interaction length—how far apart interacting cells are—is often assumed to be some value without rigorous justifications because molecules’ invisible paths and complex multicellular geometries pose challenges. Here we present an approach, combining mathematical models and experiments, for determining a chemical signal’s interaction length. With murine embryonic stem (ES) cells as a testbed, we found that differentiating ES cells secrete FGF4, among others, to communicate over many millimeters in cell culture dishes and, thereby, form a spatially extended, macroscopic entity that grows only if its centimeter-scale population density is above a threshold value. With this ‘macroscopic quorum sensing’, an isolated macroscopic, but not isolated microscopic, colony can survive differentiation. Our integrated approach can determine chemical signals’ interaction lengths in generic multicellular communities. [Figure not available: see fulltext.].
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