Researchers pooled neural progenitor cells from dozens of donors into “cell villages” to measure relative cell fitness and developed Townlet, a tool that reads each donor’s contribution within a mixed culture to map how genetics shape cellular resilience to disease and toxins.

Townlet interprets proportional donor shares over time to quantify true biological differences in fitness while accounting for the compositional data challenge that can make a shrinking share look like a biological effect.

Findings point to two genetic pathways—factors driving cell proliferation and factors driving cell survival under toxin exposure—that together influence individual brain vulnerability.

The team published their method and results in the American Journal of Human Genetics and has made Townlet’s code publicly available for broad use and replication.

In a large pooled study focusing on the autism-associated chromosome 16p11.2 deletion, cells from deletion carriers divided faster than non-carriers, implicating early brain overgrowth as a potential driver of macrocephaly in some autism cases.

This approach enables the construction of an atlas of human vulnerability, mapping how genetics shape cell fitness across cell types and exposures to guide personalized medicine and reduce reliance on animal studies.

Looking ahead, researchers aim to expand the atlas to more cell types and environmental stressors, with Townlet’s code available for other scientists to apply in diverse studies.

Townlet is publicly accessible for researchers, and future work will broaden the atlas to cover additional cell types and exposures.

Beyond proliferation, the study linked natural variation in brain cell growth rates to a region near ZFHX3, suggesting genetic influence on proliferation, while lead exposure revealed variable donor survival tied to a region near ARNT2 associated with protection against oxidative stress.

In a 39-donor test with lead exposure, researchers observed wide survival differences among donors, highlighting ARNT2-related pathways as contributors to differential toxin vulnerability.

A broader analysis across 35 donors connected proliferation-rate variation to the region near ZFHX3, which acts as a brake on cell division and may influence neuronal growth dynamics.