The significant variations in the behaviour of skeletal stem cells are not down to chance, but stem from a precise biological memory. This is demonstrated by a new study conducted by the Institute of Complex Systems of the National Research Council (CNR-ISC) and Sapienza University of Rome. The research highlights how these cells are capable of passing on crucial information to subsequent generations, information that influences their future ability to divide or to stop dividing.

At the heart of the discovery lies a concept borrowed from physics: ‘inheritance entropy’. When a stem cell divides, it generates a lineage that is very much like the branches of a family tree. Some branches continue to proliferate rapidly, whilst others cease growing after a few generations. Until now, science had been unable to clarify whether this halt was a random event or the result of a predetermined biological programme. The newly published data demonstrate that a cell’s proliferative fate is closely linked to its family history.

“The key to this discovery lies in the calculation of entropy, a concept in physics that measures the degree of disorder in a system,” says Andrea Cavagna (CNR-ISC), one of the study’s authors. “We discovered that at certain points in the family tree, an epigenetic modification is triggered – that is, a change that influences cellular behaviour without altering the DNA – which acts as a biological countdown for all future descendants.” This sort of ‘switch’ does not halt growth immediately, but has a delayed effect: the cell continues to divide for a few generations, but its descendants gradually come to a halt. “This time lag creates a highly organised pattern within the colony.” continues Cavagna. “It is precisely this surplus of order that reduces entropy, demonstrating that stem cell growth follows much more structured rules than expected, guided by ancestral memory rather than chance.”

The discovery promises to have significant implications for regenerative medicine and the study of tissue ageing. Furthermore, the concept of hereditary entropy could be applied in future cancer research to determine whether the drug resistance developed by certain cancer cells follows a similar hereditary pattern within their family tree.