Kavli Institute of Nanoscience, Delft, The Netherlands.
Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nat Chem Biol. 2023 May;19(5):596-606. doi: 10.1038/s41589-022-01225-x. Epub 2023 Jan 12.
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.
细胞可以分泌帮助彼此复制的分子。在细胞培养物中，化学信号可能仅在细胞菌落内部或菌落之间扩散。由于分子的无形路径和复杂的多细胞几何形状构成了挑战，因此，化学信号的相互作用长度（相互作用的细胞之间的距离）通常被假设为某个值，而没有严格的理由。在这里，我们提出了一种结合数学模型和实验的方法，用于确定化学信号的相互作用长度。以小鼠胚胎干细胞（ES）细胞作为试验台，我们发现分化的 ES 细胞分泌 FGF4 等分子，在细胞培养皿中传播数毫米，从而形成一个空间扩展的宏观实体，只有当其厘米级的种群密度超过阈值时才会生长。通过这种“宏观群体感应”，孤立的宏观但不是孤立的微观菌落可以存活分化。我们的综合方法可以确定通用多细胞群落中化学信号的相互作用长度。
