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Nuclei multiplexing with barcoded antibodies for single-nucleus genomics.
Gaublomme, Jellert T; Li, Bo; McCabe, Cristin; Knecht, Abigail; Yang, Yiming; Drokhlyansky, Eugene; Van Wittenberghe, Nicholas; Waldman, Julia; Dionne, Danielle; Nguyen, Lan; De Jager, Philip L; Yeung, Bertrand; Zhao, Xinfang; Habib, Naomi; Rozenblatt-Rosen, Orit; Regev, Aviv.
Afiliação
  • Gaublomme JT; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. jellert.gaublomme@columbia.edu.
  • Li B; Department of Biological Sciences, Columbia University, New York, NY, 10027, USA. jellert.gaublomme@columbia.edu.
  • McCabe C; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • Knecht A; Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
  • Yang Y; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • Drokhlyansky E; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • Van Wittenberghe N; Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
  • Waldman J; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • Dionne D; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • Nguyen L; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • De Jager PL; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • Yeung B; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
  • Zhao X; Center for Translational & Computational Neuroimmunology, Columbia University Medical Center, New York, NY, 10019, USA.
  • Habib N; BioLegend Inc., San Diego, CA, 92121, USA.
  • Rozenblatt-Rosen O; BioLegend Inc., San Diego, CA, 92121, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Nat Commun ; 10(1): 2907, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266958
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.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Núcleo Celular / Genômica / Análise de Célula Única / Anticorpos Limite: Idoso / Animais / Feminino / Humanos / Masculino Idioma: Inglês Revista: Nat Commun Assunto da revista: Biologia / Ciência Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Estados Unidos

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Núcleo Celular / Genômica / Análise de Célula Única / Anticorpos Limite: Idoso / Animais / Feminino / Humanos / Masculino Idioma: Inglês Revista: Nat Commun Assunto da revista: Biologia / Ciência Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Estados Unidos