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Nat Biotechnol. 2015 May;33(5):495-502. doi: 10.1038/nbt.3192. Epub 2015 Apr 13.

Spatial reconstruction of single-cell gene expression data.

Author information

1
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
2
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
3
1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA. [3] Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA. [4] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA. [5] Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
4
1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Abstract

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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PMID:
25867923
PMCID:
PMC4430369
DOI:
10.1038/nbt.3192
[Indexed for MEDLINE]
Free PMC Article

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