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Nuclei multiplexing with barcoded antibodies for single-nucleus genomics

Author

Listed:
  • Jellert T. Gaublomme

    (Broad Institute of Harvard and MIT
    Columbia University)

  • Bo Li

    (Broad Institute of Harvard and MIT
    Massachusetts General Hospital and Harvard Medical School)

  • Cristin McCabe

    (Broad Institute of Harvard and MIT)

  • Abigail Knecht

    (Broad Institute of Harvard and MIT)

  • Yiming Yang

    (Allergy, and Immunology Massachusetts General Hospital and Harvard Medical School)

  • Eugene Drokhlyansky

    (Broad Institute of Harvard and MIT)

  • Nicholas Wittenberghe

    (Broad Institute of Harvard and MIT)

  • Julia Waldman

    (Broad Institute of Harvard and MIT)

  • Danielle Dionne

    (Broad Institute of Harvard and MIT)

  • Lan Nguyen

    (Broad Institute of Harvard and MIT)

  • Philip L. De Jager

    (Columbia University Medical Center)

  • Bertrand Yeung

    (BioLegend Inc.)

  • Xinfang Zhao

    (BioLegend Inc.)

  • Naomi Habib

    (Broad Institute of Harvard and MIT
    Hebrew University of Jerusalem)

  • Orit Rozenblatt-Rosen

    (Broad Institute of Harvard and MIT)

  • Aviv Regev

    (Broad Institute of Harvard and MIT
    Massachusetts Institute of Technology)

Abstract

Single-nucleus RNA-seq (snRNA-seq) enables the interrogation of cellular states in complex tissues that are challenging to dissociate or are frozen, and opens the way to human genetics studies, clinical trials, and precise cell atlases of large organs. However, such applications are currently limited by batch effects, processing, and costs. Here, we present an approach for multiplexing snRNA-seq, using sample-barcoded antibodies to uniquely label nuclei from distinct samples. Comparing human brain cortex samples profiled with or without hashing antibodies, we demonstrate that nucleus hashing does not significantly alter recovered profiles. We develop DemuxEM, a computational tool that detects inter-sample multiplets and assigns singlets to their sample of origin, and validate its accuracy using sex-specific gene expression, species-mixing and natural genetic variation. Our approach will facilitate tissue atlases of isogenic model organisms or from multiple biopsies or longitudinal samples of one donor, and large-scale perturbation screens.

Suggested Citation

  • Jellert T. Gaublomme & Bo Li & Cristin McCabe & Abigail Knecht & Yiming Yang & Eugene Drokhlyansky & Nicholas Wittenberghe & Julia Waldman & Danielle Dionne & Lan Nguyen & Philip L. De Jager & Bertran, 2019. "Nuclei multiplexing with barcoded antibodies for single-nucleus genomics," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10756-2
    DOI: 10.1038/s41467-019-10756-2
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    Cited by:

    1. Alessandra Castiglioni & Yagai Yang & Katherine Williams & Alvin Gogineni & Ryan S. Lane & Amber W. Wang & Justin A. Shyer & Zhe Zhang & Stephanie Mittman & Alan Gutierrez & Jillian L. Astarita & Minh, 2023. "Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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