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| Status |
Public on Jan 28, 2022 |
| Title |
High Resolution Slide-seqV2 Spatial Transcriptomics Enables Discovery of Disease-Specific Cell Neighborhoods and Pathways |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| 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.
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| 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.
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| Contributor(s) |
Marshall JL, Noel T, Wang QS, Greka A |
| Citation(s) |
35372810 |
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https://www.biorxiv.org/content/10.1101/2021.10.10.463829v1
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| Submission date |
Dec 03, 2021 |
| Last update date |
Apr 07, 2022 |
| Contact name |
Jamie L Marshall |
| E-mail(s) |
jammars@gmail.com, jmarshal@broadinstitute.org
|
| Organization name |
Broad Institute
|
| Department |
Kidney Disease Initiative
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| Street address |
75 Ames Street, Office 5013C
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (85)
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| Relations |
| BioProject |
PRJNA785857 |
| SRA |
SRP349114 |
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