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Spatial host-microbiome sequencing

View ORCID ProfileBritta Lötstedt, View ORCID ProfileMartin Stražar, View ORCID ProfileRamnik Xavier, View ORCID ProfileAviv Regev, View ORCID ProfileSanja Vickovic
doi: https://doi.org/10.1101/2022.07.18.500470
Britta Lötstedt
1Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
2Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
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  • ORCID record for Britta Lötstedt
Martin Stražar
3Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Ramnik Xavier
3Broad Institute of MIT and Harvard, Cambridge, MA, USA
4Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA
5Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Aviv Regev
1Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
7Genentech, 1 DNA Way, South San Francisco, CA, USA
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  • For correspondence: svickovic@nygenome.org aviv.regev.sc@gmail.com
Sanja Vickovic
1Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
8New York Genome Center, New York, NY, USA
9Department of Biomedical Engineering and Herbert Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA
10Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Beijer Laboratory for Gene and Neuro Research, Uppsala University, Uppsala, Sweden
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  • For correspondence: svickovic@nygenome.org aviv.regev.sc@gmail.com
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ABSTRACT

Mucosal and barrier tissues such as the gut, lung or skin, are composed of a complex network of cells and microbes forming a tight niche that prevents pathogen colonization and supports host-microbiome symbiosis. Characterizing these networks at high molecular and cellular resolution is crucial for our understanding of homeostasis and disease. Spatial transcriptomics has emerged as a key technology to positionally profile RNAs at high resolution in tissues. Here, we present spatial host-microbiome sequencing, an all-sequencing based approach that captures tissue histology, polyadenylated RNAs and bacterial 16S sequences directly from tissues on spatially barcoded glass surfaces. We apply our approach to the mouse gut as a model system, use a novel deep learning approach for data mapping and detect spatial niches impacted by microbial biogeography. Spatial host-microbiome sequencing should enhance study of native host-microbe interactions in health and disease.

Competing Interest Statement

A.R. is a founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics and until August 31, 2020 was a SAB member of Syros Pharmaceuticals, Neogene Therapeutics, Asimov and ThermoFisher Scientific. From August 1, 2020, A.R. is an employee of Genentech, and equity holder in Roche. S.V is an author on patents applied for by Spatial Transcriptomics AB (10X Genomics Inc). S.V. and A.R. are co-inventors on PCT/US2020/015481 relating to this work. The remaining authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 19, 2022.
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Spatial host-microbiome sequencing
Britta Lötstedt, Martin Stražar, Ramnik Xavier, Aviv Regev, Sanja Vickovic
bioRxiv 2022.07.18.500470; doi: https://doi.org/10.1101/2022.07.18.500470
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Spatial host-microbiome sequencing
Britta Lötstedt, Martin Stražar, Ramnik Xavier, Aviv Regev, Sanja Vickovic
bioRxiv 2022.07.18.500470; doi: https://doi.org/10.1101/2022.07.18.500470

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