Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells

作者：Yu-Heng Cheng, Yu‐Chih Chen, Eric Lin, Riley Brien, Seungwon Jung, Yu-Ting Chen, Wonchoel Lee, Zhijian Hao, Saswat Sahoo, Hyun Min Kang, Jason Cong, Monika L. Burness, Sunitha Nagrath, Max S. Wicha, Euisik Yoon · 发表于：Nature Communications · 年份：2019 · DOI：10.1038/s41467-019-10122-2 · 被引用次数：231 · 研究领域：Single-cell and spatial transcriptomics、Cancer Cells and Metastasis、Cancer Genomics and Diagnostics

Molecular analysis of circulating tumor cells (CTCs) at single-cell resolution offers great promise for cancer diagnostics and therapeutics from simple liquid biopsy. Recent development of massively parallel single-cell RNA-sequencing (scRNA-seq) provides a powerful method to resolve the cellular heterogeneity from gene expression and pathway regulation analysis. However, the scarcity of CTCs and the massive contamination of blood cells limit the utility of currently available technologies. Here, we present Hydro-Seq, a scalable hydrodynamic scRNA-seq barcoding technique, for high-throughput CTC analysis. High cell-capture efficiency and contamination removal capability of Hydro-Seq enables successful scRNA-seq of 666 CTCs from 21 breast cancer patient samples at high throughput. We identify breast cancer drug targets for hormone and targeted therapies and tracked individual cells that express markers of cancer stem cells (CSCs) as well as of epithelial/mesenchymal cell state transitions. Transcriptome analysis of these cells provides insights into monitoring target therapeutics and processes underlying tumor metastasis.