Data Sheet 1_Multi-omics integration identifies Acsm2/ACSM2A deficiency as a metabolic driver of ZBP1-mediated PANoptosis in acute kidney injury.csv

Here, we integrated cross-model transcriptomics of three mechanistically distinct murine AKI models with single-cell RNA-seq, high-dimensional weighted gene co-expression network analysis, and machine learning feature selection.

This multi-omics framework identified acyl-CoA synthetase medium-chain family member 2 (Acsm2), a rate-limiting mitochondrial enzyme for medium-chain fatty acid β-oxidation, as the top conserved hub gene suppressed in injured proximal tubule cells. Acsm2/ACSM2A downregulation was confirmed in mouse AKI models and in human HK-2 cells subjected to oxygen–glucose deprivation/reperfusion (OGD/R). ACSM2A deficiency alone was sufficient to simultaneously activate apoptosis, pyroptosis, and necroptosis, indicative of PANoptosis, whereas restoration of ACSM2A expression attenuated OGD/R-induced cell death.