Cell Competition Eliminates Abnormal Cells

Research Brief

Cell Competition Eliminates Abnormal Cells

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Aneuploidy—an abnormal number of chromosomes in cells—can lead to birth defects and to cancer. Surprisingly, aneuploid cells occur in the majority of developing human embryos but are usually absent by birth—one of many observations indicating that a so-far unidentified surveillance mechanism exists to remove them.

How could organisms detect cells that contain abnormal numbers of chromosome, if the individual genes on those chromosomes are all normal? In a paper published online on April 13 in eLife, Nicholas Baker, Ph.D., and colleagues concluded that such a surveillance system involves ribosomes, the molecular “factories” that translate messenger RNA into proteins. Every chromosome in every cell carries genes that code for the many proteins (known as Rps) that form ribosomes. Aneuploidy—by creating an abnormal number of chromosomes in a cell—also changes the number of Rp genes in a cell. Therefore, a cell’s number of Rp genes might act as “readouts” of aneuploidy, which would be detected as imbalances in the amounts of different Rps.

Dr. Baker and colleagues found that this indeed was the case in developing Drosophila tissue: Normal cells (possessing their full complement of Rp genes) eliminated those aneuploid cells that were missing some of their Rp genes through the process of cell competition. If the same mechanism for eliminating aneuploid cells applies to humans, then defects in cell competition could allow aneuploid cells to accumulate, increasing rates of developmental defects and cancer; conversely, boosting cell competition could be strategy for combating cancer or even aging, which is also associated with increased aneuploidy.

Dr. Baker is professor of genetics, of developmental and molecular biology, and of ophthalmology and visual sciences. He also holds the Harold and Muriel Block Chair in Genetics.