Longitudinal Multiomic and Spatial Transcriptomic Profiling of Lupus Nephritis Progression in a Murine Model

Bulk RNA sequencing was performed on kidneys from lupus-prone female NZB/W F1 mice at 10, 20, and 30 weeks of age to characterize transcriptional changes during disease progression. Minimal differences were observed at early stages, whereas advanced disease was associated with marked upregulation of genes involved in immune activation, cytokine signaling, fibrosis, and oxidative stress.

Spatial transcriptomic profiling of 30-week kidneys further resolved the spatial organization of these transcriptional changes, identifying nine distinct spatial clusters with unique gene expression signatures. Spatial molecular signature analysis revealed localized inflammatory programs enriched for cytokine/chemokine and interferon signaling pathways.