Macroscopic quorum sensing sustains differentiating embryonic stem cells

Hirad Daneshpour, Pim van den Bersselaar, Chun Hao Chao, Thomas G. Fazzio, Hyun Youk*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)
3 Downloads (Pure)


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.].

Original languageEnglish
Pages (from-to)596-606
Number of pages11
JournalNature Chemical Biology
Issue number5
Publication statusPublished - 2023


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