Game of Clones

· Cambridge


Epithelial tissues are made of different mutant progenitor cells that divide forming clones. These clones are constantly fighting each other in order to get as much space as possible and they are increased in size and number as we age (known as “Mutational landscape”). The more mutant clones growing in the tissue, the more chances of one of these cells to get another mutation that may drive tumour formation.

Sometimes external forces (acting as selective pressures) might change the rules of this battle, making some clones to grow over the competitors. This is how Darwinian evolution works.

Among others, exposure to Low-Dose of Ionising Radiation (LDIR) is one of these selective pressures that might change the outcome of this competition by promoting oxidative stress in the cells. Using mouse oesophageal epithelium as a model, we found that under LDIR, wild type clones are lost from the tissue. However, some mutant clones are adapted to this new environment and they proliferate more, conquering free space left by wild types and expanding massively.

When we modulate the environmental factors that help wild type clones to survive, we make this competition more equilibrated and promote mutant clones to be expelled from the tissue, before the latest give rise to cancer.