Spatial reconstruction of single-cell gene expression data

Spatial localization is a key determinant of cellular fate and behavior, but methods for spatially resolved, transcriptome-wide gene expression profiling across complex tissues are lacking. RNA staining methods assay only a small number of transcripts, whereas single-cell RNA-seq, which measures glo...

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Main Authors: Satija, Rahul, Farrell, Jeffrey A, Gennert, David, Schier, Alexander F, Regev, Aviv
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Nature Publishing Group 2016
Online Access:http://hdl.handle.net/1721.1/105746
https://orcid.org/0000-0001-8567-2049
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author Satija, Rahul
Farrell, Jeffrey A
Gennert, David
Schier, Alexander F
Regev, Aviv
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Satija, Rahul
Farrell, Jeffrey A
Gennert, David
Schier, Alexander F
Regev, Aviv
author_sort Satija, Rahul
collection MIT
description Spatial localization is a key determinant of cellular fate and behavior, but methods for spatially resolved, transcriptome-wide gene expression profiling across complex tissues are lacking. RNA staining methods assay only a small number of transcripts, whereas single-cell RNA-seq, which measures global gene expression, separates cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos and generated a transcriptome-wide map of spatial patterning. We confirmed Seurat's accuracy using several experimental approaches, then used the strategy to identify a set of archetypal expression patterns and spatial markers. Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems.
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spelling mit-1721.1/1057462022-10-01T13:16:56Z Spatial reconstruction of single-cell gene expression data Satija, Rahul Farrell, Jeffrey A Gennert, David Schier, Alexander F Regev, Aviv Massachusetts Institute of Technology. Department of Biology Regev, Aviv Spatial localization is a key determinant of cellular fate and behavior, but methods for spatially resolved, transcriptome-wide gene expression profiling across complex tissues are lacking. RNA staining methods assay only a small number of transcripts, whereas single-cell RNA-seq, which measures global gene expression, separates cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos and generated a transcriptome-wide map of spatial patterning. We confirmed Seurat's accuracy using several experimental approaches, then used the strategy to identify a set of archetypal expression patterns and spatial markers. Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems. Howard Hughes Medical Institute Klarman Cell Observatory National Human Genome Research Institute (U.S.) (Centers for Excellence in Genomics Science 1P50HG006193) 2016-12-07T20:58:05Z 2016-12-07T20:58:05Z 2015-04 2014-09 Article http://purl.org/eprint/type/JournalArticle 1087-0156 1546-1696 http://hdl.handle.net/1721.1/105746 Satija, Rahul et al. “Spatial Reconstruction of Single-Cell Gene Expression Data.” Nature Biotechnology 33.5 (2015): 495–502. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1038/nbt.3192 Nature Biotechnology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC
spellingShingle Satija, Rahul
Farrell, Jeffrey A
Gennert, David
Schier, Alexander F
Regev, Aviv
Spatial reconstruction of single-cell gene expression data
title Spatial reconstruction of single-cell gene expression data
title_full Spatial reconstruction of single-cell gene expression data
title_fullStr Spatial reconstruction of single-cell gene expression data
title_full_unstemmed Spatial reconstruction of single-cell gene expression data
title_short Spatial reconstruction of single-cell gene expression data
title_sort spatial reconstruction of single cell gene expression data
url http://hdl.handle.net/1721.1/105746
https://orcid.org/0000-0001-8567-2049
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AT schieralexanderf spatialreconstructionofsinglecellgeneexpressiondata
AT regevaviv spatialreconstructionofsinglecellgeneexpressiondata