| Experiment Id | GSE190094 | Name | High Resolution Slide-seqV2 Spatial Transcriptomics Enables Discovery of Disease-Specific Cell Neighborhoods and Pathways |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-02-09 |
| description | High resolution spatial transcriptomics is a transformative technology that enables mapping of RNA expression directly from intact tissue sections; however, its utility for the elucidation of disease processes and therapeutically actionable pathways remain largely unexplored. Here we applied Slide-seqV2 to mouse and human kidneys, in healthy and in distinct disease paradigms. First, we established the feasibility of Slide-seqV2 in human kidney by analyzing tissue from 9 distinct donors, 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 also found perturbations in 77 genes associated with the unfolded protein response (UPR), including Tmed9. Treatment with a TMED9-targeting compound showed efficient removal of toxic mutant proteins and reversal of the UPR. Our studies illustrate and experimentally validate the utility of Slide-seqV2 for the discovery of disease-specific cell neighborhoods and actionable targets. For the BTBR experiments, the BTBR-wt/wt are controls and BTBR-ob/ob are diabetic samples. Seven arrays per mouse and 4 mice of each gentoptype were processed. For the UMOD experiments, UMOD-WT are controls and UMOD-KI are ADTKD samples. Five arrays per mouse and 3 WT mice and 5 KI mice were processed. There are 3 separate files types: BAMs, raw data which is unmapped spatial data, and processed data which contains QCed and mapped kidney cell types. |
