Project description:The human kidneys are comprised of multiple different cell types in a complex anatomical arragemnt that is optimal for their key functions such as waste removal, regulation of fluid and electrolyte homeostasis and production of hormones. In chronic kidney disease (CKD) this arrangement is disrupted with de-differentiation and atrophy of epithelial cells, recruitment of immune cells and activation of myofibroblasts to produce excess scarring. A better understanding of cellular phenotypes, complex intercellular communication and intracellular signaling pathways that promote CKD could lead to development of novel therapies. We applied single-cell spatial transcriptomics (CosMx Spatial molecular imaging) to human kidney neprectomy speciemens with unilateral ureteral obstruction (UUO, n=5) and healthy kidneys (n=2).
Project description:The human kidneys are comprised of multiple different cell types in a complex anatomical arragemnt that is optimal for their key functions such as waste removal, regulation of fluid and electrolyte homeostasis and production of hormones. In chronic kidney disease (CKD) this arrangement is disrupted with de-differentiation and atrophy of epithelial cells, recruitment of immune cells and activation of myofibroblasts to produce excess scarring. A better understanding of cellular phenotypes, complex intercellular communication and intracellular signaling pathways that promote CKD could lead to development of novel therapies. We applied single-cell spatial transcriptomics (CosMx Spatial molecular imaging) to human kidney biopy and nephrectomy samples from patients with IgA nephropathy (n=6), minimal change disease (n=3) and advanced pyelonephritis (n=4).
Project description:Diffuse large B-cell lymphomas (DLBCLs) are a common and heterogeneous group of mature B-cell malignancies that typically arise in lymph nodes; sites in which stromal and endothelial cells, antigen-presenting cells and other myeloid cells facilitate adaptive immune responses by T-cells and B-cells against pathogens. In this study, we have leveraged the spatial transcriptomic platform of CosMx together with CODEX imaging technology to investigate the spatial immunology and pathobiology of DLBCL.
Project description:Inflammatory bowel diseases (IBDs) including ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory diseases with increasing worldwide prevalence that show a perplexing heterogeneity in manifestations and response to treatment. We applied spatial transcriptomics at single-cell resolution (CosMx Spatial Molecular Imaging) to human inflamed and uninflamed intestine.
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:Buffy coat PBMC RNA expression was tested using a custom Nanostring probe panel, to identify general immune and glucocorticoid receptor-associated immune genes. ClinicalTrials.gov Identifier: NCT00824941