GSDMD transcript levels are higher in endothelial than cardiomyocyte compartments across three human heart cohorts

Authors

Oryoji, D., Doi, G., Fujimoto, S., Nishimura, N., Otsuka, K., Kuwahara, A., Ayano, M., Kimoto, Y., Akashi, K., Niiro, H., Mitoma, H.

Abstract

Cardiac GSDMD research has largely centred on cardiomyocytes. We quantified donor-level endothelial-minus-cardiomyocyte differences in two single-nucleus cohorts and one GeoMx spatial cohort, retaining assay-specific scales. GSDMD was higher in endothelial compartments in 42/42, 38/38 and 27/32 donors and ranked, post hoc, at the 94.9th, 95.1st and 97.4th percentiles of the corresponding within-cohort signed-contrast distributions. Although positive direction and complete donor concordance were not unique transcriptome-wide, this hypothesis-led target retained high rank across markedly different reference backgrounds and assay modalities. A fixed eight-transcript panel included both endothelial- and cardiomyocyte-shifted members, arguing against a uniform panel-wide directional shift or simple detection failure. GeoMx provided the most discriminating transcriptome background but remained composition-sensitive. GSDMD transcripts are therefore recurrently higher in endothelial than cardiomyocyte compartments across human-heart cohorts, showing that a cardiomyocyte-only interpretation of human-heart GSDMD transcript signals is incomplete.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 11 Sep 2026.

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