New Tech Shows How Embryos Eliminate Defective Cells

Scientists have developed molecular scissors that can create and track cells with missing or extra chromosomes in living tissue, offering new insights into how human embryos naturally eliminate genetic defects before birth.

The research reveals that embryonic cell survival depends not just on internal genetic problems, but on a complex cellular competition where neighboring cells actively push defective ones toward death.

When Cellular Instruction Manuals Go Missing

More than 80% of early human embryos contain cells with the wrong number of chromosomes—a condition called aneuploidy that typically causes miscarriages or developmental disorders when it persists. But healthy babies are born because embryos somehow identify and eliminate these problematic cells before implantation.

Dr. Marco Milán’s team at IRB Barcelona has now created a tool that generates customized chromosome imbalances in fruit fly tissue, allowing researchers to watch in real-time how cells respond to genetic deficits. “We can select which bit of the genome we want to alter and can immediately observe how cells respond,” explains Dr. Milán, an ICREA researcher at IRB Barcelona.

The study, published in Cell Genomics, reveals that cells missing one chromosome copy—called monosomic cells—lose dozens or hundreds of key genes simultaneously. When these cells suddenly can’t produce enough essential proteins, they become weak players within the tissue.

The Cellular Duel That Determines Survival

What happens next surprised the researchers. Rather than simply dying from internal problems, these weakened cells face elimination through a process called cell competition, where fitter neighboring cells literally push aneuploid cells toward programmed death.

“We found that the ‘fittest’ cells literally push aneuplodies towards apoptosis; if these aneuploid cells are left alone, they can survive,” says Dr. Elena Fusari, first author of the study and recipient of a “la Caixa” fellowship.

The researchers discovered three distinct types of cellular competition. In classic competition, normal cells outcompete defective ones. In “super-competition,” cells with extra chromosomes grow faster while accelerating the removal of cells with missing chromosomes. Most dramatically, in “lethal competition,” the presence of neighboring cells with chromosome gains turns survivable genetic defects into certain death.

Beyond Ribosomal Proteins

Previous research focused heavily on ribosomal protein genes—the cellular machinery that makes other proteins—as the main culprits when cells lose chromosome copies. But this study reveals the genome contains many more dosage-sensitive regions than previously recognized.

The researchers systematically tested a chromosome region spanning 1,750 genes that was thought to be free of problematic areas. Yet they found multiple regions where losing just one copy caused growth problems and cellular competition. Some effects came from single genes, while others resulted from the cumulative impact of losing multiple genes simultaneously.

Notably, cells carrying extra copies of up to 1,500 genes showed no major growth problems on their own—contradicting findings from laboratory cell cultures where chromosome gains typically impair growth.

Implications for Fertility Treatment

The findings could reshape how fertility clinics select embryos for implantation. Currently, IVF clinics typically discard embryos with high levels of chromosome abnormalities.

“In the field of assisted reproduction, there’s a growing reconsideration of current embryo selection criteria. This shift comes as new research suggests that embryos may actually be capable of eliminating problematic cells on their own,” says Dr. Fusari.

The research suggests that embryos’ natural ability to eliminate defective cells might be more robust than previously thought, potentially allowing some embryos currently discarded to develop normally.

Cancer Connections

Understanding cellular competition rules may also advance cancer treatment, since 90% of solid tumors contain cells with chromosome abnormalities. The researchers plan to map which genes trigger competition signals and explore whether this knowledge could help develop therapies that encourage healthy tissue to eliminate cancer cells.

The team’s next step involves an exhaustive search of chromosome regions that cause cellular competition. “The goal is to map which genes trigger competition signals and how we can modulate this response,” concludes Dr. Milán.

This knowledge could ultimately increase success rates in assisted reproduction and lead to new strategies for targeting the chromosome instability that characterizes many tumors.