High Resolution Slide-seqV2 Spatial Transcriptomics Enables Discovery of Disease-Specific Cell Neighborhoods and Pathways(Dataset ID: STDS0000163)

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PMID: 35372810 (IF:5.8 Q1)
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Dataset information
Summary:
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.
Overall design:
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.
Technology:
Slide-seqV2
Platform:
Illumina NovaSeq 6000 (Mus musculus)
Species:
Mus musculus(mm10)
Tissues:
Kidney
Organ parts:
Cortex,Medulla,Renal pelvis
Development stage:
6 months
Disease:
Control
Submission date: 2021-12-03Update date: 2022-04-07
Sample number: 85
DOI: To be continue
Contributors
Marshall, Jamie L,Noel, Teia,Wang, Qingbo S,Greka, Anna
Accessions
GEO Series Accessions: GSE190094
How to cite
  • Cite database of STOmicsDB:
    [1] Xu, Zhicheng et al. "STOmicsDB: a comprehensive database for spatial transcriptomics data sharing, analysis and visualization." Nucleic acids research vol. 52,D1 (2024): D1053-D1061. doi: 10.1093/nar/gkad933'
  • Cite visualization dataset:
    [2] Marshall, Jamie L,Noel, Teia,Wang, Qingbo S,Greka, Anna. High Resolution Slide-seqV2 Spatial Transcriptomics Enables Discovery of Disease-Specific Cell Neighborhoods and Pathways[DS/OL]. STOmicsDB, 2021[2021-12-03]. https://db.cngb.org/stomics/datasets/STDS0000163/. doi: xxxxxx
    #Format: {contributors}. {title}[DS/OL]. STOmicsDB, {the year of submission data}[{submission data}]. {dataset link}. doi: {doi ID}
  • Cite original data article:
    Citation: Marshall, Jamie L et al. “High-resolution Slide-seqV2 spatial transcriptomics enables discovery of disease-specific cell neighborhoods and pathways.” iScience vol. 25,4 104097. 16 Mar. 2022, doi:10.1016/j.isci.2022.104097