Identification of spatially associated subpopulations by combining scRNAseq and sequential fluorescence in situ hybridization data

Combining single-cell RNA-seq with sequential single-molecule FISH defines the influence of spatial location on cell identity. How intrinsic gene-regulatory networks interact with a cell's spatial environment to define its identity remains poorly understood. We developed an approach to distingu...

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Bibliographic Details
Published in:Nature biotechnology 2018-12, Vol.36 (12), p.1183-1190
Main Authors: Zhu, Qian, Shah, Sheel, Dries, Ruben, Cai, Long, Yuan, Guo-Cheng
Format: Article
Language:English
Subjects:
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Agriculture
Analysis
Biochemistry
Bioinformatics
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Brain
Fluorescence
Fluorescence in situ hybridization
Gene expression
Gene regulation
Gene sequencing
Genes
Genetic regulation
Genetic research
Glutamatergic transmission
Heterogeneity
In situ hybridization
Life Sciences
Mapping
Markov chains
Neuroimaging
Ribonucleic acid
RNA
RNA sequencing
Signatures
Subpopulations
Visual cortex
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Summary:Combining single-cell RNA-seq with sequential single-molecule FISH defines the influence of spatial location on cell identity. How intrinsic gene-regulatory networks interact with a cell's spatial environment to define its identity remains poorly understood. We developed an approach to distinguish between intrinsic and extrinsic effects on global gene expression by integrating analysis of sequencing-based and imaging-based single-cell transcriptomic profiles, using cross-platform cell type mapping combined with a hidden Markov random field model. We applied this approach to dissect the cell-type- and spatial-domain-associated heterogeneity in the mouse visual cortex region. Our analysis identified distinct spatially associated, cell-type-independent signatures in the glutamatergic and astrocyte cell compartments. Using these signatures to analyze single-cell RNA sequencing data, we identified previously unknown spatially associated subpopulations, which were validated by comparison with anatomical structures and Allen Brain Atlas images.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt.4260