2026/05/22 by Erica Boni, Hélène Siboulet, Giacomo Ceracchini +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Bacterial biofilms and quorum sensing #Bacterial Genetics and Biotechnology #Gene Regulatory Network Analysis
paper · doi:10.7554/elife.110624.1
In nature, complex multicellular structures originate from individual cells containing all essential information for differentiation, patterning and morphogenesis. Synthetic biology enables a bottom-up approach to study these processes by engineering and combining individual modules to progressively increase the system’s complexity. Here, we engineered a multi-step differentiation program in the model prokaryote Escherichia coli. Starting from genetically identical cells and without providing any external positional information, we generated autonomous spatial patterns of colonies on a solid surface. We first employed a toggle switch to break population homogeneity (symmetry breaking), stochastically differentiating cells into two subpopulations: senders and receivers. Next, we enabled further differentiation of receiver colonies located in close proximity to sender colonies via quorum-sensing based communication (paracrine signaling). Finally, the newly emerged population matured into a different cell type via an orthogonal, self-activating, quorum sensing signal (autocrine signaling). The diversity of spatial patterns generated by this multi-step program was accurately captured by simulations of a corresponding mathematical model. Together, these results demonstrate that multi-step differentiation programs can be engineered in unicellular bacteria to drive fully self-organized spatial pattern formation.