Hodge Rachel A, Bach Erika A
Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Life (Basel). 2024 Oct 1;14(10):1251. doi: 10.3390/life14101251.
In this review, we introduce the concept of cell competition, which occurs between heterogeneous neighboring cell populations. Cells with higher relative fitness become "winners" that outcompete cells of lower relative fitness ("losers"). We discuss the idea of super-competitors, mutant cells that expand at the expense of wild-type cells. Work on adult stem cells (ASCs) has revealed principles of neutral competition, wherein ASCs can be stochastically lost and replaced, and of biased competition, in which a winning ASC with a competitive advantage replaces its neighbors. Germline stem cells (GSCs) are ASCs that are uniquely endowed with the ability to produce gametes and, therefore, impact the next generation. Mechanisms of GSC competition have been elucidated by studies in gonads, tunicates, and the mammalian testis. Competition between ASCs is thought to underlie various forms of cancer, including spermatocytic tumors in the human testis. Paternal age effect (PAE) disorders are caused by de novo mutations in human GSCs that increase their competitive ability and make them more likely to be inherited, leading to skeletal and craniofacial abnormalities in offspring. Given its widespread effects on human health, it is important to study GSC competition to elucidate how cells can become winners or losers.
在本综述中，我们介绍细胞竞争的概念，它发生在异质性相邻细胞群体之间。相对适应性较高的细胞成为“赢家”，它们胜过相对适应性较低的细胞（“输家”）。我们讨论了超级竞争者的概念，即突变细胞以牺牲野生型细胞为代价进行扩张。对成体干细胞（ASC）的研究揭示了中性竞争和偏向性竞争的原理，其中中性竞争是指ASC可能会随机丢失并被替代，而偏向性竞争是指具有竞争优势的获胜ASC会取代其邻居。生殖系干细胞（GSC）是一种特殊的ASC，具有产生配子的独特能力，因此会影响下一代。通过对性腺、被囊动物和哺乳动物睾丸的研究，已经阐明了GSC竞争的机制。ASC之间的竞争被认为是包括人类睾丸精母细胞瘤在内的各种癌症的基础。父系年龄效应（PAE）疾病是由人类GSC中的新生突变引起的，这些突变增加了它们的竞争能力，使其更有可能被遗传，从而导致后代出现骨骼和颅面异常。鉴于其对人类健康的广泛影响，研究GSC竞争以阐明细胞如何成为赢家或输家非常重要。
