To advance our understanding of cellular host-pathogen interactions, technologies that facilitate the co-capture of both host and pathogen spatial transcriptome information are needed. Here, we present an approach to simultaneously capture host and pathogen spatial gene expression information from the same formalin-fixed paraffin embedded (FFPE) tissue section using the spatial transcriptomics technology. We applied the method to COVID-19 patient lung samples and enabled the dual detection of human and SARS-CoV-2 transcriptomes at 55 μm resolution. We validated our spatial detection of SARS-CoV-2 and identified an average specificity of 94.92% in comparison to RNAScope and 82.20% in comparison to in situ sequencing (ISS). COVID-19 tissues showed an upregulation of host immune response, such as increased expression of inflammatory cytokines, lymphocyte and fibroblast markers. Our colocalization analysis revealed that SARS-CoV-2 + spots presented shifts in host RNA metabolism, autophagy, NFκB, and interferon response pathways. Future applications of our approach will enable new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes.

Impairment of the central nervous system (CNS) functions in astronauts is a major health risk for long-duration space missions. Here, for the first time, we combine single-cell multiomics (transcriptomics and chromatin accessibility) and spatial transcriptomics analyses to discover spaceflight-mediated changes in the mouse brain. By comparing ground control and spaceflight animals, we found that the main processes affected by spaceflight include neurogenesis, synaptogenesis and synaptic transmission in cortex, hippocampus, striatum and neuroendocrine structures as well as astrocyte activation and immune dysfunction. At the pathway level, spaceflight resembles neurodegenerative diseases with oxidative stress and protein misfolding components, such as in Parkinson’s disease. Our integrated spatial multiomics approach reveals both widespread and localized brain impairments and suggests key structures and mechanisms to be targeted for countermeasure development. All datasets can be mined through an interactive data portal as well as the National Aeronautics and Space Administration (NASA) GeneLab repositories.

Several important human infectious diseases are caused by microscale-sized parasitic nematodes like filarial worms. Filarial worms have their own spatial tissue organization and to uncover this tissue structure, we need methods that can spatially resolve these miniature specimens. Most filarial worms evolved a mutualistic association with endosymbiotic bacteriaWolbachia, however, the mechanisms underlying the dependency of filarial worms on the fitness of these bacteria remain unknown. AsWolbachiais essential for the development, reproduction, and survival of filarial worms, we focused on studying a posterior region containing reproductive tissue and developing embryos of adult femaleBrugia malayiworms. To spatially explore howWolbachiainteracts with the worm's reproductive system, we performed a spatial characterization using Spatial Transcriptomics (ST) across our region of interest. We provide a proof-of-concept for miniature-ST to explore spatial gene expression patterns in small sample types, demonstrating the method's ability to uncover nuanced tissue region expression patterns, observe the spatial localization of keyB. malayi-Wolbachiapathway genes, and co-localize theB. malayispatial transcriptome inWolbachiatissue regions. We envision our approach to open up new scenarios for the study of infectious diseases caused by micro-scale parasitic worms.