First Author | Marshall JL | Year | 2022 |
Journal | iScience | Volume | 25 |
Issue | 4 | Pages | 104097 |
PubMed ID | 35372810 | Mgi Jnum | J:323360 |
Mgi Id | MGI:7261050 | Doi | 10.1016/j.isci.2022.104097 |
Citation | Marshall JL, et al. (2022) High-resolution Slide-seqV2 spatial transcriptomics enables discovery of disease-specific cell neighborhoods and pathways. iScience 25(4):104097 |
abstractText | High-resolution spatial transcriptomics enables mapping of RNA expression directly from intact tissue sections; however, its utility for the elucidation of disease processes and therapeutically actionable pathways remains unexplored. We applied Slide-seqV2 to mouse and human kidneys, in healthy and distinct disease paradigms. First, we established the feasibility of Slide-seqV2 in tissue from nine distinct human kidneys, which revealed a cell neighborhood centered around a population of LYVE1+ macrophages. Second, in a mouse model of diabetic kidney disease, we detected changes in the cellular organization of the spatially restricted kidney filter and blood-flow-regulating apparatus. Third, in a mouse model of a toxic proteinopathy, we identified previously unknown, disease-specific cell neighborhoods centered around macrophages. In a spatially restricted subpopulation of epithelial cells, we discovered perturbations in 77 genes associated with the unfolded protein response. Our studies illustrate and experimentally validate the utility of Slide-seqV2 for the discovery of disease-specific cell neighborhoods. |