Macroscopic quorum sensing sustains differentiating embryonic stem cells

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.

The osteoconductive properties of graphene-based material surfaces are finely tuned by the conditioning layer and surface chemistry

“…75 Specifically, the range of cell-cell communication is mainly limited to the immediate proximity, influencing the differentiation of cells that is affected by direct cell-cell contacts. 76 As reported in Fig. 5B, the surface becomes extremely irregular and therefore we hypothesize an uneven distribution of serum protein which reflects the cell adhesion and therefore clustering (refer to Fig.…”

The salt-and-pepper pattern in mouse blastocysts is compatible with signaling beyond the nearest neighbors

“…On a timescale of several days, FGF4 has been shown to diffuse over many millimetres in cell culture dishes and that embryonic stem cells use it for communication across these large scales. 37 For a timescale of 12 h, FGF4 signaling reaches mainly first and second neighbors in embryonic stem cell cultures. 35 FGF/MAPK signaling range can be modulated by several mechanisms: FGF diffusion via heparan sulfate proteoglycans at the extracellular matrix, FGFR trafficking, and fgf4 mRNA decay.…”

The salt-and-pepper pattern in mouse blastocysts is compatible with signalling beyond the nearest neighbours

“…The main signal in this context is FGF4 11 and it is usually assumed that it freely diffuses within the tissue. On a timescale of several days, FGF4 has been shown to diffuse over many millimetres in cell culture dishes and that embryonic stem cells use it for communication across these large scales 32 . For a timescale of 12 h, FGF4 signalling reaches mainly first and second neighbours in embryonic stem cell cultures 30 .…”