Identical cells randomly choose their developmental fate

During embryonic development, cells must decide what type of cell to become: a cardiac muscle cell, a neuron, or an immune cell. How that decision is made is not fully understood. For a long time, the cell’s environment was thought to be decisive. But identical cells in the same environment sometimes still choose different paths.

Researchers used the social amoeba (Dictyostelium discoideum) as a model system. This organism is particularly well suited to such questions: it is simple, easy to manipulate, and its cells display the same phenomenon of identity choices as mammalian cells.

Randomness as a biological mechanism

What the study shows is that cells are prepared for a particular fate before the actual cell division occurs. That preparation (called lineage priming) is partly random and partly governed by fixed molecular programs. It is not one or the other: both factors work together.

Variation in cell choices is not a flaw in the system. Evolutionarily it offers an advantage: if all cells respond identically to a changing environment, an organism is more vulnerable than one with natural variation in how its cells respond.

Relevance for aging

During aging, the way cells make identity choices changes. Stem cells become less reliable at producing the right cell types at the right time. Whether that is due to shifts in the random component, the fixed component, or both, is an open question this type of research helps to address.

Direct clinical applications are still a long way off. But understanding how cell identity is established is a necessary prerequisite for developing therapies that guide cell differentiation in disease and aging.