UCLA scientists have developed a new method called cell villages to study genetic differences in cell fitness. By pooling neural progenitor cells from dozens of donors into a single culture, researchers can grow them under identical conditions. This eliminates the technical noise often found when growing cells in separate dishes.
The team also introduced a statistical tool named Townlet to analyze the data. This tool distinguishes between real biological differences and data artifacts that arise from proportional modeling. When one donor's cells take up more space in the dish, others appear to shrink by default. Townlet accounts for this to provide a reliable readout.
Researchers tested this approach on chromosome 16p11.2 deletion, which is linked to autism and macrocephaly. The study revealed that cells with this deletion divide significantly faster than those without it. This provides a mechanistic explanation for early brain overgrowth observed in some autism cases.
Beyond development, the researchers used cell villages to study how different people respond to toxic exposure. When exposed to lead, cell viability varied from a 20% drop to a 90% drop among different donors. This variation points toward a genetic basis for vulnerability to environmental toxins.
This platform reduces reliance on animal models and offers a path toward more personalized medicine. The team has made the Townlet code available for other researchers, with the ultimate goal of building an atlas of human genetic vulnerability.