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

Yu Heng Cheng, Yu Chih Chen, Eric Lin, Riley Brien, Seungwon Jung, Yu Ting Chen, Woncheol Lee, Zhijian Hao, Saswat Sahoo, Hyun Min Kang, Jason Cong, Monika Burness, Sunitha Nagrath, Max S. Wicha, Euisik Yoon

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19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2163
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Cheng, Y. H., Chen, Y. C., Lin, E., Brien, R., Jung, S., Chen, Y. T., Lee, W., Hao, Z., Sahoo, S., Min Kang, H., Cong, J., Burness, M., Nagrath, S., S. Wicha, M., & Yoon, E. (2019). Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells. Nature communications, 10(1), [2163]. https://doi.org/10.1038/s41467-019-10122-2