Project description:Plastic pollution poses a universal yet understudied environmental risk to the immune system. Once ingested, nano- and microplastic particles (MNPs) can translocate from the gut into internal organs, likely via circulation. In humans, MNPs have been detected in macrophages within carotid artery plaques, suggesting that these highly phagocytic cells, may also serve as key targets for MNPs under homeostatic conditions. Kupffer cells (KCs), the liver-resident macrophages, play a crucial role in liver homeostasis by regulating metabolism, clearing opsonized target cells, and serving as the first line of defence against bacteria. Residing within the liver sinusoids, they continuously monitor the bloodstream, efficiently capturing and eliminating pathogens and circulating particles to maintain immune and metabolic balance5. It remains unknown whether KCs efficiently capture and store MNPs and how this might affect liver function. Here, we utilize a mouse model of chronic plastic exposure to assess how ingested MNP influence KC core functions, and thereby also liver function. We show that KCs are the primary hepatic target of MNPs and that 12 weeks of exposure alters their transcriptome and impairs phagocytic capacity, leading to dysregulated liver metabolism. Microplastics, but not nanoplastics, exposure reduces KC-mediated clearance of circulating cells and bacteria and exacerbates diet-induced obesity. These findings suggest that chronic MNP exposure disrupts tissue-specific macrophage functions in a size-dependent manner, with distinct long-term consequences for liver function and overall health.
Project description:To investigate the effecs of commensal papillomavirus immunity on the homeostasis of highly mutated normal skin, spatial transcriptomics (Xenium, 10x Genomics, Pleasanton, CA) was performed on SKH-1 mouse back skin. The mice were treated with mouse papillomavirus (MmuPV1) or virus-like particles (VLP), followed by UV exposure for 25 weeks.
Project description:Recent work has shown that the spatial organization of immune responses is a critical determinant of anti-tumor immunity. Here, we profiled ten head and neck squamous cell carcinoma (HNSCC) patient tumors and one ameloblastoma tumor using Xenium V1 spatial transcriptomics. The 10X genomics human multi-tissue and cancer gene expression panel targeting 377 genes was used in combination with 100 custom Xenium probes targeting patient-specific CDR3 regions of T cell receptors (TCRs) in T cells, additoinal T cell specific genes, HPV oncoprotein genes, and tumor genes of interest. This enabled the detection of 477 transcripts within each tumor sample at a single-cell resolution. For seven of the ten HNSCC samples, different tissue sections run on different days were analyzed as technical replicates. Together, these findings introduce a scalable platform for spatial clonal T cell analysis and provide new insight into the spatial relationship of cells within the HNSCC tumor microenvironment.
Project description:Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, and gene signatures associated with pathological features, and are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmark the performance of three commercial iST platforms—10X Xenium, Vizgen MERSCOPE, and Nanostring CosMx—on serial sections from tissue microarrays (TMAs) containing 17 tumor and 16 normal tissue types for both relative technical and biological performance. On matched genes, we find that Xenium consistently generates higher transcript counts per gene without sacrificing specificity. Xenium and CosMx measure RNA transcripts in concordance with orthogonal single-cell transcriptomics. All three platforms can perform spatially resolved cell typing with varying degrees of sub-clustering capabilities, with Xenium and CosMx finding slightly more clusters than MERSCOPE, albeit with different false discovery rates and cell segmentation error frequencies. Taken together, our analyses provide a comprehensive benchmark to guide the choice of iST method as researchers design studies with precious samples in this rapidly evolving field.
Project description:One of the most common origins of Peritoneal metastasis (PM) is colon cancer, which occurs in about 20% of colon cancer patients. Given the cancer cell heterogeneity in PM, we first tried to dissect the spatial distribution of CAF and the associated niches at a single cell resolution, we exploited the Xenium In Situ high-plex spatial imaging platform. We performed the Xenium assays with 8 human PM samples of colon origin including one PM-adjacent tissue. Among the 8 PM samples, 3 samples carried a distinct iCMS3 epithelial signature (PM1, PM2, PM3), 2 carried iCMS2 signature (PM6, PM7), while the other 2 samples had a mix of both iCMS2 and iCMS3 signatures (PM4, PM5). We found that the presence of iCMS3 cancer cells was associated with an increase infiltration of lymphocytes and the formation of tertiary lymphoid structures (TLS).
Project description:Cellular plasticity is a hallmark of rare Claudin-low (CL) and metaplastic (MBC) breast cancer subtypes, with a documented overlap whose exact extent is yet unknown, and which are associated to resistance and poor survival. We used spatial transcriptomics to further characterise these plastic subtypes, respectively defined molecularly and histopathologically. We identified 3 putative CL tumours (CL-like) and 4 genomically unstable TNBC samples via molecular analyses, combined with 4 MBCs identified by a breast pathologist.