Cultures of cell lines are frequently described as the workhorses of medical research — and, like all animals, these ubiquitous biological tools can have their differences. Experiments with cells that work in one lab, or even in one batch, can fail or give different results in another. This can be down to mislabelling, and even contamination (see Nature 520, 264; 2015). In Nature this week, scientists highlight another reason: genetic variability in the same cell line (U. Ben-David et al. Nature 560, 325–330; 2018).
The researchers analysed cell lines from different sources, including the popular MCF7 type used to investigate cancer. They found a staggering amount of variation. Supposedly identical cell lines were actually far from identical — there were differences in their genomes, gene expression, morphology and, importantly, drug sensitivity. This could help to explain why so many experimental results that rely on the standard performance of a specific cell line can’t be reproduced.
The cause is genetic drift — the cell lines diverge as they are independently and individually passaged, or subcultured. It isn’t an unexpected finding, but has never been shown before on such a scale. It will still probably come as a shock to many researchers: all cell-line strains are not equal. And some are more unequal than others.