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Fujimura, Y.

Publications and source records attributed to Fujimura, Y..

5 recordsLinked to original sources

Dietary soy shapes murine microbiota to consolidate the mucosal IgA response through T follicular helper cells

The commensal microbiota plays a crucial role in shaping mucosal immunity, particularly in the induction of T follicular helper (Tfh) cells and IgA production. Here, we demonstrate that dietary soy elicits a robust Tfh cell and IgA response in Peyers patches of weaning mice. Soy feeding promotes the expansion of two principal commensal bacterial species, Limosilactobacillus reuteri and Muribaculum intestinale. Mechanistically, L. reuteri provides cognate antigens for Tfh cell activation, while M. intestinale functions as an adjuvant by promoting IL-1{beta} production from myeloid cells. The resulting IgA exhibits polyreactivity and enhances protection against Salmonella infection. These findings highlight the specific interplay among dietary components, intestinal microbiota, and mucosal immunity, thereby establishing a diet-microbe-immune axis that shapes host defense in early life. This axis represents a promising therapeutic target for developing novel strategies to enhance resistance to enteric pathogens. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=170 HEIGHT=200 SRC="FIGDIR/small/669459v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1ae8277org.highwire.dtl.DTLVardef@1f787ceorg.highwire.dtl.DTLVardef@1f51fd6org.highwire.dtl.DTLVardef@1fd3439_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDietary soy promotes T follicular helper (Tfh) cell and IgA responses in the Peyers patches of weaning mice. C_LIO_LISoy enhances the colonization of two key commensals, Limosilactobacillus reuteri and Muribaculum intestinale, in the small intestine. C_LIO_LIThese two bacteria synergize to drive mucosal immunity: L. reuteri provides cognate antigens, while M. intestinale provides an adjuvant signal by promoting IL-1{beta} production from myeloid cells. C_LIO_LISoy-induced IgA is polyreactive and protects against Salmonella infection. C_LI

immunology↗

Machine learning-based estimation of spatial gene expression pattern during ESC-derived retinal organoid development

Organoids, which can reproduce the complex tissue structures found in embryos, are revolutionizing basic research and regenerative medicine. In order to use organoids for research and medicine, it is necessary to assess the composition and arrangement of cell types within the organoid, i.e., spatial gene expression. However, current methods are invasive and require gene editing and immunostaining. In this study, we developed a non-invasive estimation method of spatial gene expression patterns using machine learning. A deep learning model was trained with an encoder-decoder architecture on a dataset of retinal organoids derived from mouse embryonic stem cells. This method successfully estimated spatially plausible fluorescent patterns with appropriate intensities, enabling the non-invasive, quantitative estimation of spatial gene expression patterns within each tissue. Thus, this method could lead to new avenues for evaluating spatial gene expression patterns across a wide range of biology and medicine fields. HighlightsO_LIA non-invasive estimation method of spatial gene expression pattern is proposed C_LIO_LIA CNN architecture is employed to convert a phase-contrast to fluorescence image C_LIO_LIThe method was trained on a dataset of mouse ESC-derived retinal organoids C_LIO_LISpatially plausible patterns of Rx gene expressions were successfully estimated C_LI

developmental biology↗

Subepidermal blisters are healed by wedge-shaped keratinocytes of hair follicle origin

Injury in adult tissue generally reactivates developmental programs to foster regeneration, but it is not known whether this paradigm applies to growing tissue. Here, by employing blisters, we show that epidermal wounds heal at the expense of skin development. The regenerated epidermis suppresses the expression of tissue morphogenesis genes accompanied by delayed hair follicle (HF) growth. Lineage tracing experiments, cell proliferation dynamics, and mathematical modeling reveal that the progeny of HF junctional zone stem cells, which undergo a morphological transformation, repair the blisters while not promoting HF development. In contrast, the contribution of interfollicular stem cell progeny to blister healing is small. These findings demonstrate that tissue development can be sacrificed for the sake of wound regeneration and suggest that tissue repair does not coincide with the reactivation of developmental programs in all regenerative contexts. Our study elucidates the key cellular mechanism of wound healing in skin blistering diseases.

cell biology↗

Merger of Betula tatewakiana (Betulaceae) from northern Japan to northeast Asian B. ovalifolia based on ploidy level

It has been controversial whether Betula tatewakiana, a dwarf birch distributed in Hokkaido of northern Japan, is an endemic species or a synonym of B. ovalifolia broadly distributed in northeast Asia. The endemic hypothesis is based on the idea that B. tatewakiana is diploid while B. ovalifolia is tetraploid and that they are separated based on the ploidy level; however no chromosome data have actually been published before. Resolving the taxonomic problem is crucial also in judging the conservation priority of B. tatewakiana in a global perspective. Our chromosome observation revealed that B. tatewakiana is tetraploid as well as B. ovalifolia. Collaterally, we conducted morphological observation and clarified that B. tatewakiana is morphologically identical to B. ovalifolia in white hairs and dense resinous glands respectively on adaxial and abaxial leaf surfaces, based on which they are different from closely related species in the same section Fruticosae. We concluded that the hypothesis that B. tatewakiana is a Hokkaido endemic based on the ploidy level is not supported and that B. tatewakiana should be merged with B. ovalifolia.

plant biology↗

Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis

The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases (IBDs); however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin not only establishes a first-line barrier against pathogens, but also serves as a niche for microbial growth. We hypothesized that dysbiosis may cause abnormal mucin utilization and microbial metabolic dysfunction. To test this hypothesis, we analyzed short-chain fatty acids (SCFAs) and mucin components in the stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohns disease (CD) patients from Japan. The levels of n-butyrate were significantly lower in the stools of both the CD and UC patients than in those of the healthy subjects. Correlation analysis identified 7 bacterial species positively correlated with n-butyrate levels, among which the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans act as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in the colonic lamina propria. Importantly, the availability of mucin-associated O-glycans to the microbiota was significantly reduced in n-butyrate-deficient UC patients. Taken together, our findings highlight the biological significance of the symbiosynthesis pathway in the production of n-butyrate, which maintains gut immune homeostasis.

microbiology↗