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Decomposing spatially dependent and cell type specific contributions to cellular heterogeneity

Qian Zhu, Sheel Shah, Ruben Dries, Long Cai, Guo-Cheng Yuan
doi: https://doi.org/10.1101/275156
Qian Zhu
1Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health, Boston, MA 02215, USA
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Sheel Shah
2Division of Biology and Biological Engineering, Caltech, Pasadena USA 91125
3UCLA-Caltech Medical Scientist Training Program, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA
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Ruben Dries
1Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health, Boston, MA 02215, USA
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Long Cai
2Division of Biology and Biological Engineering, Caltech, Pasadena USA 91125
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  • For correspondence: lcai@caltech.edu gcyuan@jimmy.harvard.edu
Guo-Cheng Yuan
1Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health, Boston, MA 02215, USA
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  • For correspondence: lcai@caltech.edu gcyuan@jimmy.harvard.edu
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Abstract

Both the intrinsic regulatory network and spatial environment are contributors of cellular identity and result in cell state variations. However, their individual contributions remain poorly understood. Here we present a systematic approach to integrate both sequencing-and imaging-based single-cell transcriptomic profiles, thereby combining whole-transcriptomic and spatial information from these assays. We applied this approach to dissect the cell-type and spatial domain associated heterogeneity within the mouse visual cortex region. Our analysis identified distinct spatially associated signatures within glutamatergic and astrocyte cell compartments, indicating strong interactions between cells and their spatial environment. Using these signatures as a guide to analyze single cell RNAseq data, we identified previously unknown, but spatially associated subpopulations. As such, our integrated approach provides a powerful tool for dissecting the roles of intrinsic regulatory networks and spatial environment in the maintenance of cellular states.

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Posted September 07, 2018.
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Decomposing spatially dependent and cell type specific contributions to cellular heterogeneity
Qian Zhu, Sheel Shah, Ruben Dries, Long Cai, Guo-Cheng Yuan
bioRxiv 275156; doi: https://doi.org/10.1101/275156
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Decomposing spatially dependent and cell type specific contributions to cellular heterogeneity
Qian Zhu, Sheel Shah, Ruben Dries, Long Cai, Guo-Cheng Yuan
bioRxiv 275156; doi: https://doi.org/10.1101/275156

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