STOmics technology:10x Genomics Visium

Data type:Spatial transcriptomics

Sample scope:Multiisolate

Summary:This study utilized 10x Visium HD spatial transcriptomics to profile sagittal sections of kidneys from control, H1N1-infected, and SARS-CoV-2-infected mouse models, investigating the association between renal zonation and viral pathogenesis. Spatial mapping of transcriptomic data defined eleven major cell clusters and accurately annotated them to distinct anatomical regions of the kidney. We further identified three spatially resolved subtypes of proximal tubule cells (PTCs): an S1 cluster (marked by Slc5a2, Slc5a12) in the cortical labyrinth, an S2 cluster (marked by Slc22a6, Slc13a3) in the cortical labyrinth-medullary ray transition region, and an S3 cluster (marked by Slc5a10, Atp11a) in the medullary ray. Analysis revealed a gradient of injury, with severity increasing from S1 to S3, as evidenced by the zonal upregulation of injury biomarkers Havcr1 (KIM-1) and Nqo. To define the cell death pathways underlying this zonated injury, we applied the AddModuleScore analysis to assess key mechanisms. While multiple forms of cell death were detected, ferroptosis demonstrated the highest activity score in infected mice. Crucially, ferroptosis activity was exclusively and significantly enriched within the corticomedullary junction (CMJ), the region where the vulnerable S3 PTCs are localized. In contrast, apoptosis, necroptosis, and pyroptosis lacked this distinct spatial preference. In conclusion, our spatial transcriptomics analysis pinpoints the selective induction of ferroptosis in the medullary ray S3 PTCs as the dominant and spatially restricted cell death signature driving viral-associated acute kidney injury, providing a novel mechanistic insight into the zonated pathology of viral nephropathies.

Contributor(s):Qingyu Li.

Submitter:李擎宇,AMMS

Release date:2026-10-01

Updated:2026-10-01