Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections

Hailey Sounart; Enikő Lázár; Yuvarani Masarapu; Jian Wu; Tibor Várkonyi; Tibor Glasz; András Kiss; Erik Borgström; Andrew Hill; Sefanit Rezene; Soham Gupta; Aleksandra Jurek; Anezka Niesnerová; Henrik Druid; Olaf Bergmann; Stefania Giacomello

doi:10.1186/s13059-023-03080-y

Dual spatially resolved transcriptomics for human host-pathogen colocalization studies in FFPE tissue sections

Genome Biol. 2023 Oct 19;24(1):237. doi: 10.1186/s13059-023-03080-y.

Authors

Hailey Sounart^#¹, Enikő Lázár^#^{1

2}, Yuvarani Masarapu¹, Jian Wu¹, Tibor Várkonyi³, Tibor Glasz³, András Kiss³, Erik Borgström⁴, Andrew Hill⁴, Sefanit Rezene⁵, Soham Gupta⁵, Aleksandra Jurek⁴, Anezka Niesnerová⁴, Henrik Druid⁶, Olaf Bergmann^#^{2

7

8}, Stefania Giacomello^#⁹

Affiliations

¹ Department of Gene Technology, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.
² Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
³ 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
⁴ 10X Genomics, Pleasanton, CA, USA.
⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Oncology-Pathology, Karolinska Institutet, 17177, Stockholm, Sweden.
⁷ Center for Regenerative Therapies Dresden (CRTD), TU Dresden, Dresden, Germany.
⁸ Universitätsmedizin Göttingen, Institute of Pharmacology and Toxicology, Göttingen, Germany.
⁹ Department of Gene Technology, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden. stefania.giacomello@scilifelab.se.

^# Contributed equally.

Abstract

Technologies to study localized host-pathogen interactions are urgently needed. Here, we present a spatial transcriptomics approach to simultaneously capture host and pathogen transcriptome-wide spatial gene expression information from human formalin-fixed paraffin-embedded (FFPE) tissue sections at a near single-cell resolution. We demonstrate this methodology in lung samples from COVID-19 patients and validate our spatial detection of SARS-CoV-2 against RNAScope and in situ sequencing. Host-pathogen colocalization analysis identified putative modulators of SARS-CoV-2 infection in human lung cells. Our approach provides new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes in FFPE samples.

Keywords: Colocalization analysis; Formalin-fixed paraffin-embedded (FFPE) tissues; Host–pathogen interactions; Spatial transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Formaldehyde
Humans
SARS-CoV-2
Tissue Fixation
Transcriptome*

Substances

Formaldehyde