Cancer is a disease that stems from a fundamental liability inherent to multicellular life forms in which an individual cell is capable of reneging on the interests of the collective organism. Although cancer is commonly described as an evolutionary process, a less appreciated aspect of tumorigenesis may be the constraints imposed by the organism’s developmental programs. Recent work from single-cell transcriptomic analyses across a range of cancer types has revealed the recurrence, plasticity, and co-option of distinct cellular states among cancer cell populations. Here, we note that across diverse cancer types, the observed cell states are proximate within the developmental hierarchy of the cell of origin. We thus posit a model by which cancer cell states are directly constrained by the organism's “developmental map.” According to this model, a population of cancer cells traverses the developmental map, thereby generating a heterogeneous set of states whose interactions underpin emergent tumor behavior.
癌症是一种疾病，源于多细胞生命形式固有的基本缺陷，其中单个细胞能够背弃集体有机体的利益。尽管癌症通常被描述为一个进化过程，但肿瘤发生中一个较少被认识的方面可能是有机体发育程序所施加的限制。最近通过单细胞转录组分析对一系列癌症类型的研究揭示了癌细胞群体中不同细胞状态的重现性、可塑性和共用。在此，我们注意到，在不同癌症类型中，观察到的细胞状态在起源细胞的发育层次中是邻近的。因此，我们提出一个模型，其中癌细胞状态直接受到有机体“发育图谱”的约束。根据这一模型，癌细胞群体遍历发育图谱，从而产生一组异质性状态，这些状态之间的相互作用支撑着涌现的肿瘤行为。
A developmental constraint model of cancer cell states and tumor heterogeneity
肿瘤(癌症)患者之家