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

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 wor...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2023-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-39367-8
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author 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
author_facet 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
author_sort Rene Yu-Hong Cheng
collection DOAJ
description 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.
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spelling doaj-art-d6f5adbaa8db45bda83806a93d331da52025-08-20T02:15:11ZengNature PortfolioNature Communications2041-17232023-06-0114111510.1038/s41467-023-39367-8SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cellsRene Yu-Hong Cheng0Joseph de Rutte1Cade Ellis K. Ito2Andee R. Ott3Lucie Bosler4Wei-Ying Kuo5Jesse Liang6Brian E. Hall7David J. Rawlings8Dino Di Carlo9Richard G. James10Center of Immunotherapy and Immunity, Seattle Children Research InstitutePartillion BioscienceCenter of Immunotherapy and Immunity, Seattle Children Research InstituteCenter of Immunotherapy and Immunity, Seattle Children Research InstitutePartillion BiosciencePartillion BiosciencePartillion BioscienceLuminex corporationCenter of Immunotherapy and Immunity, Seattle Children Research InstitutePartillion BioscienceCenter of Immunotherapy and Immunity, Seattle Children Research InstituteAbstract 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.https://doi.org/10.1038/s41467-023-39367-8
spellingShingle 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
SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
Nature Communications
title SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
title_full SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
title_fullStr SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
title_full_unstemmed SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
title_short SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
title_sort sec seq association of molecular signatures with antibody secretion in thousands of single human plasma cells
url https://doi.org/10.1038/s41467-023-39367-8
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