一千种肿瘤的瘤内转录异质性标志

2023-06-25 09:15

综上所述，我们构建了一个全面的癌症单细胞RNA测序数据集(可通过Curated Cancer Cell Atlas网站获取)，并利用该数据集进行了转录ITH的系统化描述。

SCI

24 June 2023

Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours

(NATURE; IF：69.504)

Gavish A, Tyler M, Greenwald AC, et al. Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours. Nature. Jun 2023;618(7965):598-606

Correspondence to：itay.tirosh@weizmann.ac.il

Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics. 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 ITH. 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 pancancer 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.

每个肿瘤包含不同的细胞状态，这些状态是肿瘤异质性(ITH)的基础，而ITH是癌症治疗的核心挑战。最近的几十项研究已经开始通过单细胞RNA测序来描述ITH，但每项研究通常只描述了少数肿瘤，并提供了转录ITH的不全面的见解。在这里，我们整理、注释和整合了来自77项不同研究的数据，以揭示涵盖24种肿瘤类型的1,163个肿瘤样本的转录ITH模式。在恶性细胞中，我们确定了41个一致的元程序，每个程序都由数十个基因组成，这些基因在许多肿瘤的细胞亚群中协同上调。这些元程序涵盖了不同的细胞过程，包括通用的(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个特征。大多数癌细胞的元程序与非恶性上皮细胞中的元程序相似，这表明大部分恶性ITH程序甚至在肿瘤发生之前就已经是可变的，这反映了它们的细胞起源的生物学特性。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，并利用这些来绘制肿瘤微环境中的细胞-细胞相互作用。综上所述，我们构建了一个全面的癌症单细胞RNA测序数据集(可通过Curated Cancer Cell Atlas网站获取)，并利用该数据集进行了转录ITH的系统化描述。