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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-05

AUTHORS

Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar

ABSTRACT

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. More... »

PAGES

708

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3818

    DOI

    http://dx.doi.org/10.1038/ng.3818

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084129156

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28319088


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