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

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

doi:10.64898/2026.09.06.749635

bioRxiv · 10.64898/2026.09.06.749635

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

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

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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.

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Oryoji, D., Doi, G., Fujimoto, S., Nishimura, N., Otsuka, K., Kuwahara, A., Ayano, M., Kimoto, Y., Akashi, K., Niiro, H., Mitoma, H.. 2026-09-10. GSDMD transcript levels are higher in endothelial than cardiomyocyte compartments across three human heart cohorts. https://doi.org/10.64898/2026.09.06.749635

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