Nuclei multiplexing with barcoded antibodies for single-nucleus genomics

Jellert T. Gaublomme*, Bo Li, Cristin McCabe, Abigail Knecht, Yiming Yang, Eugene Drokhlyansky, Nicholas Van Wittenberghe, Julia Waldman, Danielle Dionne, Lan Nguyen, Philip L. De Jager, Bertrand Yeung, Xinfang Zhao, Naomi Habib, Orit Rozenblatt-Rosen, Aviv Regev

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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.

Original languageAmerican English
Article number2907
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019

Bibliographical note

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

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