Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics¹. Dozens of recent studies have begun to describe ITH by single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH². Here we curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, we identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that we map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. We further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell–cell interactions within the tumour microenvironment. In summary, we have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.

每个肿瘤都包含不同的细胞状态，这些状态是肿瘤内异质性 (ITH) 的基础，这是癌症治疗的一个核心挑战¹。最近有数十项研究已开始通过单细胞 RNA 测序来描述 ITH，但每项研究通常只描绘了少量肿瘤，并且提供了转录 ITH 的狭隘观点²。在这里，我们整理、注释和整合来自 77 项不同研究的数据，以揭示涵盖 24 种肿瘤类型的 1,163 个肿瘤样本中的转录 ITH 模式。在恶性细胞中，我们确定了 41 个共有元程序，每个元程序由数十个基因组成，这些基因在许多肿瘤的细胞亚群中协调上调。这些元程序涵盖了不同的细胞过程，包括通用模式（例如细胞周期和应激）和谱系特异性模式，我们将这些模式映射到转录 ITH 的 11 个标志中。大多数癌细胞的元程序与非恶性上皮细胞中鉴定的元程序相似，这表明大部分恶性 ITH 程序甚至在肿瘤发生之前就已经发生变化，反映了其细胞来源的生物学特性。我们进一步将元程序分析扩展到六种常见的非恶性细胞类型，并利用它们来绘制肿瘤微环境中的细胞间相互作用。总之，我们组装了一个全面的泛癌单细胞 RNA 测序数据集，可通过 Curated Cancer Cell Atlas 网站获取，并利用该数据集对转录 ITH 进行系统表征。