Biology subjects

Uchiyama, K.

Publications and source records attributed to Uchiyama, K..

9 recordsLinked to original sources

bioRxiv2026

Microbiota-derived pantothenic acid rapidly restores colonic mucus barrier after antibiotic-induced dysbiosis

The intestinal mucus layer forms the primary physical barrier separating the host epithelium from the gut microbiota. Antibiotic-induced dysbiosis compromises this barrier, yet the microbial metabolites and host mechanisms responsible for its rapid restoration remain poorly understood. Here, we identify pantothenic acid (vitamin B5) as a microbial metabolite that rapidly restores colonic mucus integrity following antibiotic administration. Integrated 16S rRNA gene sequencing and metabolomic profiling of murine feces revealed a positive association between Muribaculaceae abundance, fecal pantothenic acid level, and colonic mucus thickness. Among four isolated Muribaculaceae species, only Sangeribacter muris produced pantothenic acid. An exogenous pantothenic acid supplement quickly restored the thin mucus layer. This rapid response occurred without detectable transcriptional activation. This response did not recur in isolated colonic epithelium or colonic organoids, indicating that pantothenic acid acts through a non-epithelial, non-autonomous mechanism. Together, these findings identify a previously unrecognized microbe-metabolite-host signaling pathway that rapidly regulates colonic mucus barrier homeostasis and reveal a local barrier-protective function of microbiota-derived pantothenic acid.

microbiology↗

bioRxiv2026

Genetic legacy in soil seedbanks after grassland conversion to plantation forests: evidence from Potentilla freyniana

Semi-natural grasslands are important ecosystems supporting biodiversity in Japan, but their area has declined rapidly due to land-use change and abandonment of traditional management practices such as mowing and burning. Although the conservation of genetic diversity is essential for the long-term persistence of grassland plants, little is known about the genetic diversity retained in soil seedbanks following conversion of grasslands to plantation forests. In this study, we compared the genetic diversity and population structure of above-ground and soil seedbank populations of the grassland perennial forb Potentilla freyniana across three sites in each of three land-use types: burned grasslands, deciduous plantation forests, and evergreen plantation forests (plantation ages approximately 21-62 years) on the Kaida Plateau, central Japan. Soil seedbank populations were obtained from soil samples through germination experiments, and genetic analyses were conducted using newly developed simple sequence repeat (SSR) markers. Genetic diversity was assessed using expected heterozygosity, allelic richness, and private allelic richness, population structure was evaluated using analysis of molecular variance (AMOVA), STRUCTURE analyses, and pairwise FST. Soil seedbank populations maintained levels of genetic diversity comparable to those of above-ground populations, and no significant differences were detected between the two population types. Furthermore, soil seedbank populations in evergreen plantation forests, where above-ground individuals of P. freyniana were absent, retained genetic diversity comparable to that observed in burned grasslands. AMOVA detected no significant genetic differentiation between above-ground and soil seedbank populations. These results suggest that high levels of genetic diversity can persist in soil seedbank populations for decades after forest establishment and highlight the potential importance of soil seedbanks as genetic resources for grassland restoration.

ecology↗

bioRxiv2025

A skeletal muscle-sympathetic nerve-intestine network underlies muscle inflammation and atrophy induced by immobilization

Immobility is a common cause of muscle atrophy, but the underlying mechanisms have remained unclear. Here we show that limb immobilization in mice elicits inflammation and atrophy of skeletal muscle that are preventable by neutralizing antibodies to the chemokine CXCL10. Limb immobilization also induced changes to the gut microbiota and intestinal inflammation, and either sterilization of the intestine with antibiotics or administration of 10-hydroxy-cis-12-octadecenoic acid--a linoleic acid-derived gut microbial metabolite--prevented intestinal and muscle inflammation as well as muscle atrophy induced by immobilization, implicating intestinal inflammation in muscle inflammation and atrophy. Limb immobilization activated sympathetic nerves and increased {beta}2-adrenergic receptor gene (Adrb2) expression in the intestine. Single-cell RNA-sequencing analysis revealed that, among cells expressing Adrb2 in the intestine, immobilization increased only the population of macrophages. Pharmacological inhibition or macrophage-specific ablation of Adrb2 prevented immobilization-induced intestinal and muscle inflammation. Our results thus implicate a previously unrecognized muscle-nerve-intestine network in immobilization-induced muscle atrophy.

molecular biology↗

bioRxiv2025

Transcriptome differentiation in Cryptomeria japonica trees with different origins growing in the north and south of Japan

Cryptomeria japonica is a coniferous species widely distributed throughout Japan and therefore adapted to various environments. To seek genes involved in the local adaptation of this species, individuals with different origins growing at three common gardens located in the south, central and north of Japan were subjected to transcriptome analysis. The transcriptome assembly, guided by whole-genome sequence of C. japonica, resulted in 77,212 transcripts from 56,203 genes. Individuals were clustered into three genetic groups based on single nucleotide polymorphisms (SNPs) detected in 12,389 genes among them. Weighted gene co-expression network analysis (WGCNA) identified 25 gene modules. Comparison of representative gene expression patterns for each co-expression gene module with genetic differentiation predicted by SNPs revealed that one module exhibited a negative correlation and another a positive correlation across all three common gardens. While defense response genes were highly expressed in individuals from the Pacific Ocean side of Japan (omote-sugi), terpenoid metabolism genes were more expressed in individuals originating from the Sea of Japan side (ura-sugi). These results suggest that local adaptation associated with the alteration of gene regulation occurred in biotic stress response genes in C. japonica.

plant biology↗

bioRxiv2024

Temporal continuity of habitat strengthens covariation between plant and arbuscular mycorrhizal fungal communities

Old grassland is considered one of the most biodiverse terrestrial ecosystems. The habitat temporal continuity may promote the accumulation of host species and symbiont arbuscular mycorrhizal fungi (AMF) diversity and strengthen symbiont interactions. We tested the hypothesis that covariation between AMF and plant communities is stronger in old grasslands. We compared the relationship between AMF and plant communities in forests and in new and old semi-natural grasslands in Japan. DNA was extracted from bulk roots collected at each site and from roots of Miscanthus sinensis at each grassland site. AMF operational taxonomic unit was characterized on the basis of small subunit rRNA gene sequences. Old grasslands harboured the highest diversity of AMF among vegetation types. The AMF compositions were significantly related to those of plant species. The covariation of plant-AMF communities was stronger in old grasslands than in new grasslands. Individuals of M. sinensis were found to share AMF with bulk roots comprising different species. This suggests that AMF form a common mycorrhizal network among several coexisting plants of different species. Increasing AMF diversity in the shared rhizosphere has been proposed to lead to more efficient utilization of soil nutrients and to increase overall benefits of plant-AMF facilitation.

ecology↗

bioRxiv2023

Structure of the human Bre1 complex bound to the nucleosome

Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To reveal the structural basis of H2BK120 ubiquitination and its regulation, we determined the cryo-EM structure of the human Bre1 complex bound to the nucleosome. The two RING domains of Bre1A and Bre1B recognize the acidic patch and the nucleosomal DNA phosphates around SHL 6.0, which are ideally located to recruit the E2 enzyme and ubiquitin for H2BK120-specific ubiquitination. Mutational experiments suggest that the two RING domains bind in both orientations and that ubiquitination occurs when Bre1A binds to the acidic patch. Our results provide insights into the relationships between Bre1 proteins and cancer and suggest that H2B monoubiquitination can be regulated by nuclesomal DNA flexibility.

biochemistry↗

bioRxiv2023

A chromosome-level genome assembly of amodel conifer plant, the Japanese cedar,Cryptomeria japonica D. Don

Japanese cedar (Cryptomeria japonica D. Don) is the most important Japanese forest tree, occupying about 44% of artificial forests in Japan, and planted in East Asia, Azores Archipelago, and some islands in the Indian Ocean. Although the huge genome of the species (ca. 11 Gb) with abundant repeat elements might have been an obstacle for genetic analysis, the species is easily propagated by cutting, flowered by plant hormones like gibberellic acid, transformed by agrobacterium, and edited by CRISPR/Cas9. These characteristics of C. japonica are preferable to make the species a model conifer for which reference genome sequences are necessary. In this study, we report the first chromosome-level assembly for C. japonica (2n = 22) using a third generation selfed progeny with an estimated homozygosity of 0.96. Young leaf tissue was used to extract high-molecular-weight DNA (>50 kb) for HiFi PacBio long read sequencing and to construct Hi-C/Omni-C library for Illumina short read sequencing. Using the 29x and 26x genome coverage of HiFi and Illumina reads, respectively, de novo assembly resulted in 2,650 contigs (9.1 Gb in total) with N50 contig size of 12.0 Mb. The Hi-C analysis mapped 97% of the nucleotides on the 11 chromosomes. The assembly was verified by comparing with a consensus linkage map of 7,785 markers. The BUSCO analysis confirmed ~91% of conserved genes. Annotations of genes, repeat elements and synteny with other Cupressaceae and Pinaceae species were performed, providing fundamental resources for genomic research of conifers.

genomics↗

bioRxiv2021

Retrovirus-induced leukemia - hijack of T-cell activation mechanisms revealed by single-cell analysis

Human T-cell leukemia virus type 1 (HTLV-1) mainly infects CD4+ T-cells and induces chronic, persistent infection in infected individuals with some progressing to develop adult T-cell leukemia/lymphoma (ATL). Whilst HTLV-1 alters cellular differentiation, activation and survival, it is unknown whether and how these changes contribute to malignant transformation of infected T-cells. In this study, we used single-cell RNA-Seq and TCR-Seq to investigate T-cell differentiation and HTLV-1-mediated transformation processes. We analyzed 87,742 single cells from peripheral blood of 12 infected and 3 uninfected individuals. Using multiple independent bioinformatic methods, we demonstrated that naive T-cells dynamically change into activated T-cells including infected cells, which seamlessly transitioned into ATL cells characterized by clonally expanded, highly-activated T-cells. Notably, the more activated ATL cells are, the more they acquire Treg signatures. Intriguingly, HLA class II genes were uniquely induced in infected cells, further upregulated in ATL cells and was induced by viral protein Tax. Functional assays revealed that by upregulating HLA class II, HTLV-1-infected cells can act as tolerogenic antigen presenting cells (APCs) to induce anergy of antigen specific T-cells. In conclusion, our study revealed the in vivo mechanisms of HTLV-1-mediated transformation and immune escape at single-cell level. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/458291v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@38d0fdorg.highwire.dtl.DTLVardef@20cca0org.highwire.dtl.DTLVardef@15a55e2org.highwire.dtl.DTLVardef@1bca6ac_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2020

Identification and genetic diversity analysis of a male-sterile gene (MS1) in Japanese cedar (Cryptomeria japonica D. Don)

Identifying causative genes for a target trait in conifer reproduction is challenging for species lacking whole-genome sequences. In this study, we searched for the male-sterility gene (MS1) in Cryptomeria japonica, aiming to promote marker-assisted selection (MAS) of male-sterile C. japonica to reduce the pollinosis caused by pollen dispersal from artificial C. japonica forests in Japan. We searched for mRNA sequences expressed in male strobili and found the gene CJt020762, coding for a lipid transfer protein containing a 4-bp deletion specific to male-sterile individuals. We also found a 30-bp deletion by sequencing the entire gene of another individual with the ms1. All nine breeding materials with the allele ms1 had either a 4-bp or 30-bp deletion in gene CJt020762, both of which are expected to result in faulty gene transcription and function. Furthermore, the 30-bp deletion was detected from three of five individuals in the Ishinomaki natural forest. From our findings, CJt020762 was considered to be the causative gene of MS1. Thus, by performing MAS using two deletion mutations as a DNA marker, it will be possible to find novel breeding materials of C. japonica with the allele ms1 adapted to the unique environment of each region of the Japanese archipelago.

genetics↗