Human tumors are intricate ecosystems composed of diverse genetic clones and malignant cell states that evolve in a complex tumor micro-environment. Single-cell RNA-sequencing (scRNA-seq) provides a compelling strategy to dissect this intricate biology and has enabled a revolution in our ability to understand tumor biology over the last ten years. Here we reflect on this first decade of scRNA-seq in human tumors and highlight some of the powerful insights gleaned from these studies. We first focus on computational approaches for robustly defining cancer cell states and their diversity and highlight some of the most common patterns of gene expression intra-tumor heterogeneity (eITH) observed across cancer types. We then discuss ambiguities in the field in defining and naming such eITH programs. Finally, we highlight critical developments that will facilitate future research and the broader implementation of these technologies in clinical settings.

中文翻译：

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癌细胞状态：十年人类肿瘤单细胞 RNA 测序的经验教训


人类肿瘤是由在复杂的肿瘤微环境中进化的不同基因克隆和恶性细胞状态组成的复杂生态系统。单细胞 RNA 测序 (scRNA-seq) 提供了一种令人信服的策略来剖析这种复杂的生物学，并在过去十年中使我们理解肿瘤生物学的能力发生了革命。在这里，我们回顾了 scRNA-seq 在人类肿瘤中的第一个十年，并强调了从这些研究中收集到的一些强有力的见解。我们首先关注用于稳健定义癌细胞状态及其多样性的计算方法，并强调在癌症类型中观察到的一些最常见的基因表达肿瘤内异质性（eITH）模式。然后我们讨论该领域在定义和命名此类 eITH 程序方面的模糊性。最后，我们强调了将促进未来研究以及这些技术在临床环境中更广泛实施的关键发展。