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SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells

Author

Listed:
  • Rene Yu-Hong Cheng

    (Seattle Children Research Institute
    University of Washington)

  • Joseph de Rutte

    (Partillion Bioscience)

  • Cade Ellis K. Ito

    (Seattle Children Research Institute
    University of Washington)

  • Andee R. Ott

    (Seattle Children Research Institute)

  • Lucie Bosler

    (Partillion Bioscience)

  • Wei-Ying Kuo

    (Partillion Bioscience)

  • Jesse Liang

    (Partillion Bioscience)

  • Brian E. Hall

    (Luminex corporation)

  • David J. Rawlings

    (Seattle Children Research Institute
    University of Washington
    University of Washington)

  • Dino Di Carlo

    (Partillion Bioscience
    University of California - Los Angeles
    Department of Mechanical and Aerospace Engineering
    University of California - Los Angeles)

  • Richard G. James

    (Seattle Children Research Institute
    University of Washington
    University of Washington
    University of Washington)

Abstract

The secreted products of cells drive many functions in vivo; however, methods to link this functional information to surface markers and transcriptomes have been lacking. By accumulating secretions close to secreting cells held within cavity-containing hydrogel nanovials, we demonstrate workflows to analyze the amount of IgG secreted from single human B cells and link this information to surface markers and transcriptomes from the same cells. Measurements using flow cytometry and imaging flow cytometry corroborate the association between IgG secretion and CD38/CD138. By using oligonucleotide-labeled antibodies we find that upregulation of pathways for protein localization to the endoplasmic reticulum and mitochondrial oxidative phosphorylation are most associated with high IgG secretion, and uncover surrogate plasma cell surface markers (e.g., CD59) defined by the ability to secrete IgG. Altogether, this method links quantity of secretion with single-cell sequencing (SEC-seq) and enables researchers to fully explore the links between genome and function, laying the foundation for discoveries in immunology, stem cell biology, and beyond.

Suggested Citation

  • Rene Yu-Hong Cheng & Joseph de Rutte & Cade Ellis K. Ito & Andee R. Ott & Lucie Bosler & Wei-Ying Kuo & Jesse Liang & Brian E. Hall & David J. Rawlings & Dino Di Carlo & Richard G. James, 2023. "SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39367-8
    DOI: 10.1038/s41467-023-39367-8
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    References listed on IDEAS

    as
    1. Christopher D. Scharer & Dillon G. Patterson & Tian Mi & Madeline J. Price & Sakeenah L. Hicks & Jeremy M. Boss, 2020. "Antibody-secreting cell destiny emerges during the initial stages of B-cell activation," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Sindhuja Sridharan & Nils Kurzawa & Thilo Werner & Ina Günthner & Dominic Helm & Wolfgang Huber & Marcus Bantscheff & Mikhail M. Savitski, 2019. "Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    3. Rene Yu-Hong Cheng & King L. Hung & Tingting Zhang & Claire M. Stoffers & Andee R. Ott & Emmaline R. Suchland & Nathan D. Camp & Iram F. Khan & Swati Singh & Ying-Jen Yang & David J. Rawlings & Richar, 2022. "Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment in vivo," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
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    Cited by:

    1. Doyeon Koo & Xiao Cheng & Shreya Udani & Sevana Baghdasarian & Dashuai Zhu & Junlang Li & Brian Hall & Natalie Tsubamoto & Shiqi Hu & Jina Ko & Ke Cheng & Dino Di Carlo, 2024. "Optimizing cell therapy by sorting cells with high extracellular vesicle secretion," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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