Depletion of aneuploid cells is shaped by cell-to-cell interactions.

Abstract

Aneuploidy is pervasive in early human embryos but robustly dampened during development. Later in life, aneuploidy correlates with pathological conditions, including cancer. Identification of the mechanisms underlying the elimination of aneuploid cells is relevant in development and disease. We characterized the impact on cell proliferation and survival of a large collection of molecularly defined segmental monosomies and trisomies of different sizes and ranges of overlap. Our data reveal signs of outcompetition of cells carrying small monosomies in regions devoid of previously known haploinsufficient genes. Dose-dependent effects of single genes or a discrete number of genes contribute to the phenomenon of cell competition through different mechanisms. By simultaneously inducing cells carrying monosomies and trisomies of the same genomic location, we show that trisomies potentiate or alleviate the negative effects of monosomy on growth, thus revealing a key role of cell interactions in defining the in vivo elimination of aneuploid cells.