Biology subjects

Kawabata, A.

Publications and source records attributed to Kawabata, A..

4 recordsLinked to original sources

bioRxiv2026

Spatial transcriptomic analysis reveals coordinated gene expression in ovarian clear cell carcinoma and adjacent endometriosis in UK and Japanese patients

PurposeOvarian clear cell carcinoma (OCCC) is strongly associated with endometriosis and shows geographic variation in incidence. We investigated whether OCCC and adjacent endometriosis exhibit distinct transcriptional states and whether these patterns differ between United Kingdom (UK) and Japanese cohorts. Experimental DesignWe performed whole-transcriptome spatial profiling on specimens from 16 OCCC cases (8 UK, 8 Japan) in which tumor and endometriosis were both present. Gene expression was analyzed in tumor, endometriosis and stroma. ARID1A status was assessed by immunohistochemistry. ResultsMedian age was 59 years (range 26-82). 13/16 cases (81.3%) had early-stage disease. Tissue compartment rather than cohort of origin was the dominant source of variation across endometriosis and tumor regions. Endometriosis was enriched for inflammatory and immune-related pathways compared to tumor, whilst there was greater representation of chromatin and protein-DNA complex assembly pathways in tumor regions. These patterns were conserved across both cohorts and after stratification by ARID1A status. Mesenchymal-associated gene expression scores also significantly differed across stroma, endometriosis and tumor with clear compartmental separation. Cell type deconvolution analyses showed clear compositional differences between stromal and epithelial disease compartments. ConclusionsOCCC and coexisting endometriosis are transcriptionally distinct, with the dominant contrast being compartmental rather than geographic. ARID1A alone is unlikely to account for the principal spatial transcriptional states identified here. Further analyses will be required to ascertain whether these differences reflect genuine biological differences between OCCC and coexisting endometriosis or represent different stages of endometriosis-associated tumorigenesis. Translational RelevanceOvarian clear cell carcinoma often arises in association with endometriosis, yet the biological transition between these lesions remains poorly understood. Using spatial transcriptomics in matched tumor and adjacent endometriosis from Japanese and UK cohorts, we showed that endometriosis is characterized by inflammatory and antigen-presentation features, whereas tumor regions showed chromatin-organization and oncogenic transcriptional states. These patterns were largely maintained irrespective of ARID1A status and geographic background. In addition, spatial deconvolution suggested differences in local immune composition, with tumor regions showing relatively greater neutrophil- and T cell-associated signals. Together, our data suggest that OCCC and coexisting endometriosis share a spatially linked tissue context, but that tumor regions have distinct transcriptional profile and microenvironment that may be involved in the malignant transformation and inform interpretation of molecular classification in endometriosis-associated OCCC.

pathology↗

bioRxiv2025

Genomic epidemiology reveals antibiotic resistance transfer and polyclonal dissemination of Acinetobacter baumannii in a Paraguayan hospital

Acinetobacter baumannii is a major nosocomial pathogen worldwide and, specifically, in Latin America. Genomic epidemiology has been instrumental in determining the transmission dynamics of A. baumannii in many countries of the world, yet some Latin American countries have conducted no genomic epidemiology studies. Here, we conduct the first genomic epidemiology study about this pathogen in Paraguay. We sequenced 43 isolates from a big tertiary hospital in Paraguay collected from different wards in 2021 and 2022. Our genomic epidemiology analyses, including almost 200 genomes and considering the main international clones (ICs), show that IC1, IC2, IC4, IC5 and IC7 were found in the hospital. We found novel genetic variation (3 novel Sequence Types as per the Oxford MLST scheme and one as per the Pasteur scheme) within IC7. Antibiotic susceptibility tests show that all but one of the Paraguayan isolates were resistant to carbapenems. Notably, 98% were classified as multidrug-resistant. We detected plasmids in almost all the Paraguayan isolates. Furthermore, we detected cases of recent horizontal transfer of important antibiotic-resistance genes between different ICs. On a general note, our findings highlight polyclonal spreading across different hospital wards and horizontal transfer of clinically relevant antibiotic-resistance genes among the different clones. On a more local note, this is the first genomic epidemiology study of A. baumannii in Paraguay and will be a reference point for future studies in the country and the region.

microbiology↗

bioRxiv2024

Inflammatory molecules in the glomerular endothelium in mild IgA-Nephropathy identified by single-cell and spatial transcriptome

Immunoglobulin A nephropathy (IgA-N) is a primary glomerulonephritis characterized by mesangial cell proliferation and expansion. It still leads to end-stage renal disease over the long course of the disease in many patients. Although glomerular endothelial cells (GE) have been implicated in the pathogenesis of IgA-N, their role remains poorly understood. We conducted single-cell and spatial transcriptomic analysis using human specimens with mild IgA-N compared with normal. We observed the significantly higher expression of several inflammation-associated molecules which have been reported and not reported to be involved in IgA-N pathogenesis, respectively. Furthermore, we show that several important molecules were also highly expressed in GE of IgA-N at protein level by tissue immunostaining. Our analysis suggests that the characteristic pathways identified in GE that involve these molecules are associated with the progression of IgA-N. These findings offer important insights on both the pathogenesis of IgA-N and its treatment at an early stage.

bioinformatics↗

bioRxiv2023

Growth factor-free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia

Critical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or de novo growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both ex vivo and in vivo assays. In a murine femoral artery ligation model of CLI, delivery of in situ crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.

bioengineering↗