达尔文 ( Charles Darwin )在其 1859 年所发表的 《物种起源》 ( The Origin of Species )一书中提出的以自然选择( natural selection )为核心的进化论( Theory of Evolution )诞生不久即被科学界广泛接受为关于物种起源和演化的真确学说。相较于此,由德国动物学家 Wilhelm Roux 最早于 1888 年根据不同组织间细胞常常互相侵袭的观察而提出的机体发育过程中遵循自然选择规律的细胞竞争( cell competition )假说却经历了长达一个世纪的争论,直到 1975 年 Morata 和 Ripoll 在 Developmental Biology 上发表了利用果蝇核糖体蛋白 Minutes 突变体验证杂合子细胞处于竞争失利状态的实验证据才获得了普遍认同。 细胞竞争模型的核心是低竞争力的失败者( loser )细胞被邻近的胜利者( winner )细胞感知并清除,其具有三个主要特征: 1 )失败者细胞的增殖速率显著更低; 2 )对失败者细胞的清除决定与成功者细胞的接触; 3 )失败者细胞与成功者细胞的相对状态随着发育环境的改变而不断变化。目前,已有多项证据表明细胞竞争同样存在于哺乳动物发育过程中,并且可能是一种重要的抑癌机制。然而,细胞竞争作为一种细胞群体选择机制在机体发育中的潜在关键角色仍未得到详尽阐释。 2019 年 5 月 16 日,来自美国洛克菲勒大学的 Elaine Fuchs 实验室在 Nature 上发表长文 Distinct modes of cell competition shape ammalian tissue morphogenesis , 报道了皮肤发育过程中的细胞竞争现象及其生理重要性。 请翻译本文的摘要(如下): Cell competition—the sensing and elimination of less fit ‘loser’ cells by neighbouring ‘winner’ cells—was first described in Drosophila. Although cell competition has been proposed as a selection mechanism to optimize tissue and organ development, its evolutionary generality remains unclear. Here, by using live imaging, lineage tracing, single-cell transcriptomics and genetics, we identify two cell competition mechanisms that sequentially shape and maintain the architecture of stratified tissue during skin development in mice. In the single-layered epithelium of the early embryonic epidermis, winner progenitors kill and subsequently clear neighbouring loser cells by engulfment. Later, as the tissue begins to stratify, the basal layer instead expels losers through upward flux of differentiating progeny. This cell competition switch is physiologically relevant: when it is perturbed, so too is barrier formation. Our findings show that cell competition is a selective force that optimizes vertebrate tissue function, and illuminate how a tissue dynamically adjusts cell competition strategies to preserve fitness as its architectural complexity increases during morphogenesis.