Biology subjects

Sugihara, K.

Publications and source records attributed to Sugihara, K..

8 recordsLinked to original sources

bioRxiv2026

Segmented wavetrains and sites of reversal in the mouse seminiferous tubules

Mammalian spermatogenesis occurs in the seminiferous tubules, which exhibit unique spatiotemporal differentiation patterns known as cellular association patterns. In mice, these patterns can be regarded as one-dimensional wavetrains that consistently propagate inward from both ends, resulting in one or more "sites of reversal." Segmented wavetrain pattern, in which the wave propagation direction spatially switches, was observed in our previous three-species reaction-diffusion model for interspecific species difference in spermatogenic waves (Kawamura et al., 2021). However, the biological mechanisms of the formation of sites of reversal and of this directional bias, as well as the principle of pattern formation, remain unknown. Here, we refined our previous model to match the actual biological spatiotemporal scale and examined its dynamics through extensive numerical simulations. The modified model frequently generated segmented wavetrain patterns, corresponding to the sites of reversal, but without directional bias. We systematically examined possible biological mechanisms for the bias and found that tubule elongation, especially near the rete testis, most effectively accounts for the bias among the tested. Extensive simulations revealed that the segmented pattern is numerically stable, emerges more frequently in longer domains, and shows an exponential segment size distribution with a lower limit for the stably existing segment length. These explorations imply that locally emerged unidirectional wavetrains serve as building blocks to generate the stable segmented wavetrains through their interactions. HighlightsO_LISegmented wavetrains reflect sites of reversal in seminiferous tubules. C_LIO_LISegmented patterns frequently emerge but show no inherent directional bias. C_LIO_LITubule elongation may contribute to inward propagation near the rete testis. C_LIO_LISegmented wavetrains are numerically stable and more frequent in longer domains. C_LIO_LIInteractions of local unidirectional wavetrains generate stable segmented structures. C_LI

developmental biology↗

bioRxiv2025

Immune phenotype-guided identification of disease-associated pathobionts in Crohn's disease

Aberrant immune activation within the gut mucosa and gut dysbiosis have been implicated in the pathogenesis of Crohns disease (CD). However, the specific immune responses triggered by dysbiotic microbiota, as well as the bacteria responsible for this activation, remain incompletely understood. Here, using the human microbiota-associated (HMA) mouse system, we demonstrated that colonization with dysbiotic gut microbiota from CD patients specifically induces the accumulation of mononuclear phagocytes, which may drive an interleukin-1 (IL-1)-driven inflammatory signature. Moreover, we identified pathobiont strains with a potent IL-1{beta}-inducing capacity, termed IL-1{beta}-inducing pathobionts (IBIP). Isolated IBIP strains exhibit genetic and functional similarities to adherent-invasive Escherichia coli but harbor unique virulence-associated genes. Colonization with the IBIP E. coli strain exacerbated experimental colitis in an IL-1 signal-dependent manner. Notably, the colonization of IBIP E. coli can be detected by measuring the levels of specific immunoglobulin A (IgA) in their stool samples. Moreover, the level of IBIP-reactive IgA in stool may serve as a predictive biomarker for treatment response to anti-TNF therapies in treatment-naive pediatric CD patients. Altogether, IBIP colonization could help identify CD patients with inflammatory dysbiosis who are likely to be refractory to anti-TNF therapies.

immunology↗

bioRxiv2024

A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules

Changes in the gut microbiome have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a multi-cohort analysis of small molecule biosynthetic gene clusters (BGCs) in 5,306 metagenomic samples of the gut microbiome from 2,033 Inflammatory Bowel Disease (IBD) patients and 833 matched healthy subjects and identified a group of Clostridia-derived BGCs that are significantly associated with IBD. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the IBD-enriched BGCs. Using two mouse models of colitis, we show that the discovered small molecules disrupt gut permeability and exacerbate inflammation in chemically and genetically susceptible mice. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of microbiome-host interactions in the context of microbiome-associated diseases.

microbiology↗

bioRxiv2022

Mineral phase analysis of various marine-species shells and skeletons collected in Japan: Implications for marine biominerals

Mineral phase analysis was performed, using X-ray diffractometry (XRD), for marine-organism shell/skeleton samples of 146-148 extant species of the following 10 phyla (18 classes) collected in Japan: Rhodophyta (Florideophyceae), Foraminifera (Globothalamea and Tubothalamea), Porifera (Hexactinellida), Cnidaria (Anthozoa and Hydrozoa), Bryozoa (Gymnolaemata), Brachiopoda (Lingulata and Rhynchonellata), Mollusca (Bivalvia, Cephalopoda, Gastropoda and Polyplacophora), Annelida (Polychaeta), Arthropoda (Cirripedia), and Echinodermata (Asteroidea, Crinoidea and Echinoidea). Some of the species were analyzed for each specific part of their shells/skeletons. Almost all the samples exhibited any of calcite, aragonite or their mixed phase, predominantly depending on their taxonomy and shell/skeletal structures. For samples containing significant amounts of calcite, the MgCO3 wt % of calcite has been determined from their XRD data, which ranges from [~]0 to [~]15 wt % and indicates clear inter-taxonomic differences. Low MgCO3 values ([~]0-4 wt %) are observed for Rhynchonellata, Bivalvia, Gastropoda and Cirripedia; intermediate values ([~]4-8 wt %) for Cephalopoda; high values ([~]8-15 wt %) for Florideophyceae, Globothalamea, Tubothalamea, Polychaeta, Asteroidea and Crinoidea; low-to-high values for Gymnolaemata; intermediate-to-high values for Anthozoa and Echinoidea. These MgCO3 data show broad trends mostly consistent with general phylogenetic evolution (i.e. very similar patterns for each phylogenetic group). Distinct within-individual variability of the MgCO3 content is found for regular Echinoidea species (i.e. their teeth and spines have lower MgCO3 values than the other skeletal parts). Correlation of the MgCO3 content with seawater temperature is also examined/discussed for most of the above calcite-containing classes. In order to interpret our XRD-based observations of various marine-species shells/skeletons, detailed discussions are presented by comparing with previous studies and also by using knowledge of taxonomy, shell/skeletal structures, habitats, living modes and so on. The comprehensive dataset and discussions will provide useful implications for biomineralization studies.

zoology↗

bioRxiv2022

Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction

Pathobionts employ unique metabolic adaptation mechanisms to maximize their growth in disease conditions. Adherent-invasive Escherichia coli (AIEC), a pathobiont enriched in the gut mucosa of patients with inflammatory bowel disease (IBD), utilizes diet-derived L-serine to adapt to the inflamed gut. Therefore, the restriction of dietary L-serine starves AIEC and limits its fitness advantage. Here, we find that AIEC can overcome this nutrient limitation by switching the nutrient source from the diet to the host cells in the presence of mucolytic bacteria. During diet-derived L-serine restriction, the mucolytic symbiont Akkermansia muciniphila promotes the encroachment of AIEC to the epithelial niche by degrading the mucus layer. In the epithelial niche, AIEC acquires L-serine from the colonic epithelium and thus proliferates. Our work suggests that the indirect metabolic network between pathobionts and commensal symbionts enables pathobionts to overcome nutritional restriction and thrive in the gut.

microbiology↗

bioRxiv2022

Site-specific adaptation mechanisms of an oral pathobiont in the oral and gut mucosae

Periodontal inflammation leads to oral dysbiosis with the expansion of oral pathobionts. Besides the pathogenic role of oral pathobionts during periodontal inflammation, studies have revealed that oral pathobionts contribute to diseases in distant organs beyond the oral mucosa. For example, the oral pathobiont Klebsiella aerogenes, which accumulates in the oral mucosa during periodontitis in mice, can exacerbate colitis when it ectopically colonizes the gastrointestinal tract. However, the precise mechanisms by which oral pathobionts establish their colonization in extra-oral mucosal sites remains incompletely understood. We performed high-throughput in vivo genetic screening to identify fitness genes required for the adaptation of the oral pathobiont K. aerogenes to different mucosal sites - the oral and gut mucosae - at the steady state and during inflammation. In addition, the global transcriptome of K. aerogenes in different environments was analyzed. We determined that K. aerogenes employs genes related to iron acquisition and chaperone usher pili, which are encoded on a newly identified genomic locus named "locus of colonization in the inflamed gut" (LIG), for adaptation in the gut mucosa, particularly during inflammation. In contrast, the LIG virulence factors are not required for K. aerogenes to adapt to the oral mucosa. Thus, oral pathobionts likely exploit distinct adaptation mechanisms in their ectopically colonized intestinal niche compared to their original niche. Author SummaryThe symbiotic bacterial community evolves uniquely at each body site. However, under certain circumstances, symbionts may disseminate far from their original niche and colonize a site ectopically. It has been reported that oral resident bacteria associated with periodontal disease, namely oral pathobionts, contribute to gastrointestinal diseases, such as inflammatory bowel disease and colorectal cancer, through ectopic colonization of the gut. However, the molecular mechanisms by which oral pathobionts adapt to the gut environment remain largely unexplored. In this study, using a model oral pathobiont Klebsiella aerogenes, we screened genes essential for the colonization of the pathobiont at different mucosal sites. We discovered that the oral pathobiont uses distinct virulence mechanisms at two different mucosal sites - the oral and gut mucosae. Understanding the strategies of bacteria localized in ectopic organs may lead to the development of strategies to prevent disease caused by the dissemination of pathogenic oral bacteria.

microbiology↗

bioRxiv2020

A new microcirculation culture method with a self-organized capillary network

A lack of microcirculation has been one of the most significant obstacles for three-dimensional culture systems of organoids and embryonic tissues. Here, we developed a simple and reliable method to implement a perfusable capillary network in vitro. The method employed the self-organization of endothelial cells to generate a capillary network and a static pressure difference for culture medium circulation, which can be easily introduced to standard biological laboratories and enables long-term cultivation of vascular structures. Using this culture system, we perfused the lumen of the self-organized capillary network and observed a flow-induced vascular remodeling process, cell shape changes, and collective cell migration. We also observed an increase in cell proliferation around the synthetic vasculature induced by flow, indicating functional perfusion of the culture medium. We also reconstructed extravasation of tumor and inflammatory cells, and circulation inside spheroids including endothelial cells and human lung fibroblasts. In conclusion, this system is a promising tool to elucidate the mechanisms of various biological processes related to vascular flow.

cell biology↗

bioRxiv2018

MUTE Directly Orchestrates Cell State Switch and the Single Symmetric Division to Create Stomata

Precise cell division control is critical for developmental patterning. For the differentiation of a functional stoma, a cellular valve for efficient gas exchange, the single symmetric division of an immediate precursor is absolutely essential. Yet, the mechanism governing the single division event remains unclear. Here we report the complete inventories of gene expression by the Arabidopsis bHLH protein MUTE, a potent inducer of stomatal differentiation. MUTE switches the gene expression program initiated by its sister bHLH, SPEECHLESS. MUTE directly induces a suite of cell-cycle genes, including CYCD5;1, and their transcriptional repressors, FAMA and FOUR LIPS. The architecture of the regulatory network initiated by MUTE represents an Incoherent Type 1 Feed-Forward Loop. Our mathematical modeling and experimental perturbations support a notion that MUTE orchestrates a transcriptional cascade leading to the tightly-restricted, robust pulse of cell-cycle gene expression, thereby ensuring the single cell division to create functional stomata.\n\nHighlightsO_LIComplete inventories of gene expression in stomatal differentiation state are elucidated\nC_LIO_LIMUTE switches stomatal patterning program initiated by its sister bHLH, SPEECHLESS\nC_LIO_LIMUTE directly induces cell-cycle genes and their direct transcriptional repressors\nC_LIO_LIIncoherent feed-forward loop by MUTE ensures the single division of a stomatal precursor\nC_LI

plant biology↗