Fusari Elena, Muzzopappa Mariana, Gracia Juliette, Milán Marco
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain.
Cell Genom. 2025 Aug 13;5(8):100894. doi: 10.1016/j.xgen.2025.100894. Epub 2025 Jun 3.
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.
非整倍体在人类早期胚胎中普遍存在，但在发育过程中会受到强烈抑制。在生命后期，非整倍体与包括癌症在内的病理状况相关。确定消除非整倍体细胞的潜在机制在发育和疾病研究中具有重要意义。我们对大量分子定义的不同大小和重叠范围的节段性单体和三体对细胞增殖和存活的影响进行了表征。我们的数据揭示了在缺乏先前已知单倍体不足基因的区域中携带小单体的细胞被淘汰的迹象。单个基因或离散数量基因的剂量依赖性效应通过不同机制促成细胞竞争现象。通过同时诱导携带相同基因组位置单体和三体的细胞，我们表明三体增强或减轻了单体对生长的负面影响，从而揭示了细胞相互作用在确定体内非整倍体细胞消除中的关键作用。
