Scientists have developed molecular scissors that can create and track cells with missing or additional chromosomes in biological tissues, providing new insights into how human embryos naturally eliminate genetic defects before birth.
The study shows that the survival of embryonic cells depends not only on internal genetic problems, but also on neighboring cells actively turning defective cells toward complex cell competitions that die.
When the cellular instruction manual is lost
More than 80% of early human embryos contain cells with the wrong number of chromosomes – a disease called aneuploidy and usually leads to miscarriage or developmental disorders when it persists. But healthy babies are born because the embryos somehow recognize and eliminate these problematic cells before being implanted.
Dr. Marco Milán’s team at IRB Barcelona has now created a tool that creates customized chromosomal imbalances in fruit fly tissues, allowing researchers to see in real time how cells respond to genetic defects. “We can choose a portion of the genome we want to change and can immediately observe the cell’s response,” explained Dr. Milán, an IRB researcher at Barcelona.
The study, published in Cell Genomics, revealed that cells (monomer cells) that lack one chromosomal replication simultaneously reduced dozens or hundreds of key genes. When these cells suddenly fail to produce enough essential proteins, they become weak actors in the tissues.
Cellular duel for survival
What happened next surprised the researchers. Instead of simply dying from internal problems, these attenuated cells face elimination through a process called cell competition, in which shorter adjacent cells actually push aneuploid cells toward programming death.
“We found that ‘Yeopter’ cells actually push non-span animals to apoptosis; if these aneuploid cells remain alone, they can survive,” said Dr. Elena Fusari, the first author of the study and first author of the “La Caixa” scholarship.
The researchers found three different types of cell competition. In classical competition, normal cells outweigh defective cells. In “hypercompetition”, cells with additional chromosomes grow faster, while accelerating cells that lack chromosomes. In “fatal competition”, most notably, the presence of adjacent cells with chromosomal growth turns survivable genetic defects into certain deaths.
Beyond ribosomal proteins
Previous research focused on ribosomal protein genes (cellular mechanisms that produce other proteins), the main culprit when cells lose copies of chromosomes. But this study revealed that more dose-sensitive regions of the genome are known than previously.
The researchers systematically tested a chromosomal region spanning 1,750 genes, that was considered to be without problems. However, they found that losing only one copy of multiple regions can lead to growth problems and cell competition. Some effects come from a single gene, while others are caused by the loss of the cumulative effects of multiple genes simultaneously.
It is worth noting that cells carrying up to 1,500 additional copies of genes have no major growth problems themselves, thus making the discovery of paragraphs from laboratory cell cultures, where chromosomal growth often impairs growing laboratory cell cultures.
Impact on fertility treatment
These findings can reshape how fertility clinics choose embryos for implantation. Currently, IVF clinics usually discard embryos with high chromosomal abnormalities.
“In the field of assisted reproduction, current embryo selection criteria are increasingly reconsidered. This shift is new research showing that embryos may actually be able to eliminate problematic cells on their own,” said Dr. Fusari.
The study shows that embryos may have a stronger natural ability to eliminate defective cells than previously thought, which may allow some currently discarded embryos to develop normally.
Cancer Connection
Understanding cell competition rules may also drive cancer treatment, as 90% of solid tumors contain cells with chromosomal abnormalities. The researchers plan to map which genes trigger competition signals and explore whether this knowledge can help develop treatments that encourage healthy tissue to eliminate cancer cells.
The team’s next step involves a detailed search of the chromosomal regions that lead to cell competition. “The goal is to map which genes trigger competition signals and how we regulate this response,” Dr. Milán concluded.
This knowledge can ultimately increase the success rate of assisted reproduction and lead to new strategies for chromosomal instability to characterize many tumors.
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