Bonn, 16.02.2021. It is one of the great mysteries in biology - from apparently uniform stem cells, a plethora of diverse, specialized cell types arise through so called differentiation processes. Although we know that the special functions of the cells are founded in the genes, one central question still remains open: How is this differentiation process controlled? What ensures that the vital proportions of cell types are present within the population?
"The current theories of cell differentiation assume that the cell fate is determined on the level of single cells. But we see evidence for a much more complex system," says Dr. Aneta Koseska, Lise-Meitner research group leader at research center caesar. In her latest findings, which are being published in the journal “Development” and selected as a “Research highlight”, she outlines a novel theory. According to Dr. Koseska, cells do not determine their identity individually, but rather, the entire population of cells in the collective controls which specializations individual cells should form and in which proportions. "The cells of a mammalian embryo are not isolated from each other. They communicate with each other through various molecules and form a unified system. Thus, as the population grows and cells divide, the system determines at which point in time differentiation must occur in a self-organized manner," Dr. Koseska said.
Using simulations, the group of Dr. Aneta Koseska, together with Dr. Christian Schroeter (Max Planck Institute for Molecular Physiology, Dortmund, Germany) showed that the specialization of a single cell depends on the other cells in the population. If one disturbed the balance of cell types in the simulation - for example, by removing one cell type completely - the collective of cells restored the original proportions. The scientists therefore propose that cell fate decision-making and active maintenance of the most favorable population composition is based on a communication mechanism among cells, rather than on individual cell decisions.
This new theory opens the door for further studies. Dr. Koseska is confident: "Our theory provides direct predictions of the underlying mechanism that can and must now be further investigated and experimentally validated."
Stanoev, A., Schröter, C., Koseska, A. (2021). Robustness and timing of cellular differentiation through population-based symmetry breaking. Development 148, dev197608.
See the Research highlight