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

doi:10.1038/s41467-019-10122-2

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

Yonsei Advanced Science Institute

Research output: Contribution to journal › Article › peer-review

125 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 language	English
Article number	2163
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10122-2
Publication status	Published - 2019 Dec 1

Bibliographical note

Funding Information:
This work was supported in part by grants R35 CA 129765 from the NIH and from the Breast Cancer Research Foundation to M.S.W and in part by University of Michigan Coulter Translational Research Partnership Program, and in part by the grants R01 CA 203810 and R21 CA 195016 from NIH to E.Y. The support of Y.-C.C. from Forbes Institute for Cancer Discovery and the support of M.B. from FFANY (Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale ™) are acknowledged. We thank the Lurie Nanofabrication Facility of the University of Michigan (Ann Arbor, MI) for device fabrication.

Publisher Copyright:
© 2019, The Author(s).

All Science Journal Classification (ASJC) codes

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-019-10122-2

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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

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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.",

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

note = "Funding Information: This work was supported in part by grants R35 CA 129765 from the NIH and from the Breast Cancer Research Foundation to M.S.W and in part by University of Michigan Coulter Translational Research Partnership Program, and in part by the grants R01 CA 203810 and R21 CA 195016 from NIH to E.Y. The support of Y.-C.C. from Forbes Institute for Cancer Discovery and the support of M.B. from FFANY (Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale {\texttrademark}) are acknowledged. We thank the Lurie Nanofabrication Facility of the University of Michigan (Ann Arbor, MI) for device fabrication. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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