Nat Genet:单细胞分析解开结直肠癌细胞的神秘面纱

Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors

结合单细胞基因组学和计算机技术，一个研究团队（包括来自杰克逊实验室（JAx）单细胞生物学主任Paul Robson博士在内）鉴定出了11种结直肠癌肿瘤的癌细胞组成及邻近的非癌细胞。这对于更好的肿瘤靶向诊断和治疗很重要。”使用单细胞测序。”JAX科学家、这篇发表在Nature Genetics上的文章共同第一作者Elise Courtois说道。”我们可以根据肿瘤中的细胞组成将结直肠癌进一步分类。因为每种亚型的肿瘤病人生存率存在差别，我们的方法将为肿瘤医生提供更多的关于肿瘤预后和治疗的信息。”

Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs). Additionally, epithelial-mesenchymal transition (EMT)-related genes were found to be upregulated only in the CAF subpopulation of tumor samples. Notably, colorectal tumors previously assigned to a single subtype on the basis of bulk transcriptomics could be divided into subgroups with divergent survival probability by using single-cell signatures, thus underscoring the prognostic value of our approach. Overall, our results demonstrate that unbiased single-cell RNA-seq profiling of tumor and matched normal samples provides a unique opportunity to characterize aberrant cell states within a tumor.