Biology subjects

Niiro, H.

Publications and source records attributed to Niiro, H..

3 recordsLinked to original sources

bioRxiv2026

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

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.

cell biology↗

bioRxiv2026

Spatial transcriptomics identifies a translayer architecture of pyroptosis-related transcription in systemic sclerosis skin

Anatomical-layer enrichment does not establish cellular attribution, so correspondence with major-cell-class expression must be tested gene by gene. Systemic sclerosis (SSc) skin is informative because inflammasome- and pyroptosis-related molecules have been reported across epidermal, fibroblast-associated and vascular contexts. Spatial transcriptomics of SSc and control skin, with same-donor single-nucleus profiles from 10 SSc donors, revealed gene-specific correspondence. Across 13 discovery sections, NLRP1, PYCARD and CASP4 were epidermally biased, whereas GSDMD was dermally biased. An independent 10-section SSc cohort supported epidermal NLRP1 (q = 0.0078) and PYCARD (q = 0.043), with directional, non-significant support for CASP4 and GSDMD. Despite epidermal NLRP1 bias, endothelial class-pseudobulk exceeded keratinocyte class-pseudobulk in all 10 donors. Restricted three-class reconstruction reproduced the NLRP1 direction in 1 and 0 of 10 donors under the two fixed dermal weightings and in 0-8 of 10 across a post hoc sweep of the dermal endothelial share; PYCARD and GSDMD were concordant in most donors at every weighting, and CASP4 in no more than 4 of 10. Thus, tissue layer and major cell class are gene-specifically non-equivalent axes of spatial interpretation.

immunology↗

bioRxiv2023

Chronic BCR signaling generates and maintains age-associated B cells from anergic B cells

Accumulation of age-associated B cells (ABCs) with autoreactive properties contributes to the pathogenesis of autoimmune diseases1-5. However, the mechanisms whereby ABCs are generated and maintained are not understood1, 2, 4. Here, we show that continuous stimulation of the B-cell receptor (BCR) with self-antigens plays a crucial role in ABC generation from anergic B cells and that this signal is vital for sustaining ABCs during aging and autoimmunity. In ABCs, BCR signaling was constitutively activated and the surface BCR was internalized in vivo, as occurs in autoreactive B cells chronically exposed to self-antigens6. With aging, ABCs were generated from autoreactive anergic B cells, but not from B cells expressing non-self-reactive BCR. In vitro stimulation of anergic B cells with self-antigen, interleukin-21, and Toll-like receptor 7/9 agonists promoted their differentiation to ABCs. Furthermore, the cellular phenotype of ABCs in Bm12-induced lupus mice7, 8 resembled that of ABCs in aged mice, showing activation of BCR signaling, expression of activation markers, and BCR internalization. Importantly, Btk was persistently activated in ABCs of aged/autoimmune mice and humans with lupus. Pharmacological Btk inhibition resulted in a marked reduction in the number of ABCs and pathogenicity in lupus mice. Our findings have implications for accumulating ABCs and developing therapies for autoimmune diseases.

immunology↗