Biology subjects

Yamaoka, S.

Publications and source records attributed to Yamaoka, S..

14 recordsLinked to original sources

bioRxiv2025

A SABATH family enzyme regulates development via the gibberellin-related pathway in the liverwort Marchantia polymorpha

The SABATH family enzymes are a group of plant-specific methyltransferases that catalyze the methylation of many small molecules, including several plant hormones. While this family emerged anciently before the evolution of land plants from streptophyte algae, little is known about their biological function in plant lineages other than angiosperms. Here, we identified 12 SABATH family genes from the liverwort Marchantia polymorpha and found that MpSABATH2 is essential for its development. Mpsabath2 mutants were severely inhibited in thallus growth and gemma cup formation, while spontaneously forming sexual branches under non-inductive conditions. These phenotypes resembled the developmental responses to far-red light, which was also supported by transcriptome analysis. Further genetic analysis connected this phenomenon with gibberellin (GA)-related metabolism. Blocking GA biosynthesis partially rescued Mpsabath2 phenotypes, which were restored by treatment with the GA precursor, ent-kaurenoic acid. Given that bryophyte and angiosperm SABATH proteins fall into distinct phylogenetic clades, our findings suggest that SABATH family enzymes independently acquired roles in developmental regulation through convergent or parallel evolution in land plants.

plant biology↗

bioRxiv2025

MarpolBase: Genome database for Marchantia polymorpha featuring high quality reference genome sequences

The liverwort Marchantia polymorpha is a key model organism for understanding land plant evolution, development, and gene regulation. To support the growing demand for high-quality genomic resources, we present MarpolBase, a comprehensive and integrated genome database that hosts newly assembled, high-accuracy reference genomes for both the male Tak-1 and female Tak-2 accessions, designated as ver. 7.1 reference genomes. These new assemblies, generated using PacBio HiFi long-read sequencing, represent nearly telomere-to-telomere chromosome-level genomes, with improvements in assembly continuity, annotation accuracy, and structural resolution--especially for repeat-rich regions and sex chromosomes. MarpolBase offers not only access to genome sequences and gene annotations but also provides a unified platform for data exploration, comparative analysis, and community-driven gene nomenclature. It includes keyword-searchable gene pages with structural and functional annotations, expression data integration, genome browser visualization, and online analytical and utility tools. By unifying genome assembly, annotation, nomenclature, and analysis tools in a single platform, MarpolBase serves as a central resource for functional genomics and evolutionary studies in M. polymorpha, and a model for future plant genome databases.

genomics↗

bioRxiv2024

Novel Mechanism of Inflammatory Activation by Ebola Virus Matrix Protein Linked to the Ebolavirus Virulence

Uncontrolled systemic inflammatory responses are a critical pathological feature of fatal Ebola virus (EBOV) infection. While some inflammatory responses may originate from mononuclear phagocytes (MNPs), non-immune cells vastly outnumber MNPs and may be an important source of inflammation. Here, we demonstrated that highly virulent EBOV induced a high and sustained pro-inflammatory response compared to less virulent ebolaviruses in non-MNPs through TLR4-independent NF-{kappa}B activation. We identified the EBOV matrix protein VP40 as a potent activator of NF-{kappa}B in non-MNPs, whose intrinsic inflammatory activation ability is higher than VP40 proteins from less virulent ebolaviruses. This suggests that VP40 is a novel virulence determinant inducing distinct degrees of pro-inflammatory responses among ebolaviruses. Mechanistically, VP40 activated the NF-{kappa}B signaling pathway, primarily via TNFR1 using a ligand-independent mechanism. These findings reveal mechanisms that may drive systemic inflammation and promote EBOV pathogenesis, suggesting potential therapeutic strategies to mitigate immune dysregulation in severe EBOV infections.

microbiology↗

bioRxiv2023

Evolutionarily Conserved CKI1-Mediated Two-Component Signaling is Required for Female Germline Specification in Marchantia polymorpha

In land plants, gametes derive from a small number of dedicated haploid cells. 1 In angiosperms, one central cell and one egg cell are differentiated in the embryo sac as female gametes for double fertilization, while in non-flowering plants, only one egg cell is generated in the female sexual organ, called the archegonium. 2,3 The central cell specification of Arabidopsis thaliana is controlled by the histidine kinase CYTOKININ-INDEPENDENT 1 (CKI1), which is a two-component signaling (TCS) activator sharing downstream regulatory components with the cytokinin signaling pathway. 4-7 Our phylogenetic analysis suggested that CKI1 orthologs broadly exist in land plants. However, the role of CKI1 in the archegonium-bearing non-flowering plants remains unclear. Here we found that the sole CKI1 ortholog in the liverwort Marchantia polymorpha, MpCKI1, which functions through conserved downstream TCS components, regulates the female germline specification for egg cell development in the archegonium. In M. polymorpha, the archegonium develops three-dimensionally from a single cell, accumulating MpBONOBO (MpBNB), a master regulator for germline initiation and differentiation. 8 We visualized female germline specification by capturing the distribution pattern of MpBNB in the discrete stages of early archegonium development, and found that the MpBNB accumulation is restricted to female germline cells. MpCKI1 is required for the proper MpBNB accumulation in the female germline, and is critical for the asymmetric cell divisions that specify the female germline cells. These results suggest that CKI1-mediated TCS originated during early land plant evolution and participates in female germ cell specification in deeply-diverged plant lineages.

plant biology↗

bioRxiv2023

Thermospermine is an evolutionarily ancestral phytohormone required for organ development and stress responses in the basal land plant Marchantia polymorpha

Thermospermine, a structural isomer of spermine, suppresses auxin-inducible xylem differentiation, whereas spermine is implicated in stress responses in angiosperms. Thermospermine synthase ACAULIS5 (ACL5) is well conserved from algae to land plants, but its physiological function remains elusive in non-vascular plants. Here we focused on MpACL5, a gene in the liverwort Marchantia polymorpha, which rescued the dwarf phenotype of the acl5 mutant of Arabidopsis. In the Mpacl5 mutants generated by genome editing, growth of the vegetative organ, thallus, and the sexual reproductive organ, gametangiophore, was severely retarded. The mutant gametangiophore exhibited remarkable morphological defects such as short stalks, fasciation, and indeterminate growth; it was formed as a fusion of two gametangiophores and a new gametangiophore was often initiated from the old one. Furthermore, Mpacl5 was shown to be hypersensitive to heat and salt stresses. Given the absence of spermine in liverworts including M. polymorpha, these results reveal that thermospermine has a dual primordial function in organ development and stress responses in the basal land plant lineage, the latter of which may have eventually been assigned to spermine during the land plant evolution.

plant biology↗

bioRxiv2023

Biosynthesis of gibberellin-related compounds modulates far-red light responses in the liverwort Marchantia polymorpha

The phytohormone gibberellins (GAs) are key regulators of growth, development and environmental responses in angiosperms. From an evolutionary perspective, all major steps of GA biosynthesis are conserved among vascular plants, while GA biosynthetic intermediates such as ent-kaurenoic acid (KA) are also produced by bryophytes. Here we show that in the liverwort Marchantia polymorpha, KA and GA12 are synthesized by evolutionarily conserved enzymes, which are required for developmental responses to far-red light (FR). Under FR-enriched conditions, mutants of various biosynthesis enzymes consistently altered thallus growth allometry, delayed the initiation of gametogenesis, and affected the morphology of gamete-bearing structures (gametangiophores). By chemical treatments and LC-MS/MS analyses, we confirmed these phenotypes were caused by deficiency of some GA-related compounds derived from KA, but not bioactive GAs from vascular plants. Transcriptome analysis showed that FR enrichment induced the up-regulation of genes related to stress responses and secondary metabolism in M. polymorpha, which was largely dependent on the biosynthesis of GA-related compounds. Due to the lack of the canonical GA receptors in bryophytes, we hypothesize that GA-related compounds are commonly synthesized in land plants but co-opted independently to regulate responses to light quality change in different lineages during the past 450 million years of evolution.

plant biology↗

bioRxiv2023

Three-dimensional morphological analysis revealed the cell patterning bases for the sexual dimorphism development in the liverwort Marchantia polymorpha

In land plants, sexual dimorphism can develop in both diploid sporophytes and haploid gametophytes. While developmental processes of sexual dimorphism have been extensively studied in the sporophytic reproductive organs of model flowering plants such as stamens and carpels of Arabidopsis thaliana, those occurring in gametophyte generation are less well characterized due to the lack of amenable model systems. We here performed three-dimensional morphological analyses of gametophytic sexual branch differentiation in the liverwort Marchantia polymorpha, using high-depth confocal imaging and a computational cell segmentation technique. Our analysis revealed that specification of germline precursors initiates in a very early stage of sexual branch development where incipient branch primordia are barely recognizable in the apical notch region. Moreover, spatial distribution patterns of germline precursors differ between males and females from the initial stage of primordium development in a manner dependent on the master sexual differentiation regulator MpFGMYB. In later stages, distribution patterns of germline precursors predict the sex-specific gametangia arrangement and receptacle morphologies seen in mature sexual branches. Taken together, our data suggests a tightly coupled progression of germline segregation and sexual dimorphism development in M. polymorpha.

plant biology↗

bioRxiv2022

Deep learning for histopathological subtyping and grading of lung adenocarcinoma

The histopathological distinction of lung adenocarcinoma (LADC) subtypes is subject to high inter-observer variability, which can compromise the optimal assessment of the patient prognosis. Therefore, this study developed convolutional neural networks (CNNs) capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the LADC tumour grades established recently by the International Association for the Study of Lung Cancer pathology committee. Consensus LADC ground truth histopathological images were obtained from seventeen expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained with EfficientNet b3 architecture to predict eight different LADC classes (lepidic, acinar, papillary, micropapillary, solid, invasive mucinous adenocarcinoma, other carcinoma types, and no carcinoma cells). Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1-scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models. Moreover, the grading prediction of one of the trained models was more accurate than those of 14 out of 15 pulmonary pathologists involved in the study (p=0.0003). Both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained CNNs improve the diagnostic accuracy of the pathologist, standardise LADC subtype recognition, and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

pathology↗

bioRxiv2022

MarpolBase Expression: A Web-based, Comprehensive Platform for Visualization and Analysis of Transcriptomes in the Liverwort Marchantia polymorpha

The liverwort Marchantia polymorpha is equipped with a wide range of molecular and genetic tools and resources that have led to its wide use to explore the evo-devo aspects of land plants. Although its diverse transcriptome data are rapidly accumulating, there is no extensive yet user-friendly tool to exploit such a compilation of data and to summarize results with the latest annotations. Here, we have developed a web-based suite of tools, MarpolBase Expression (MBEX, https://marchantia.info/mbex/), where users can visualize gene expression profiles, identify differentially expressed genes, perform co-expression and functional enrichment analyses, and summarize their comprehensive output in various portable formats. Using oil body biogenesis as an example, we demonstrated that the results generated by MBEX were consistent with the published experimental evidence and also revealed a novel transcriptional network in this process. MBEX should facilitate the exploration and discovery of the genetic and functional networks behind various biological processes in M. polymorpha, and promote our understanding of the evolution of land plants.

plant biology↗

bioRxiv2021

A selective glucocorticoid receptor modulator attenuates lung inflammation and improves alveolarization in a neonatal rat model of bronchopulmonary dysplasia.

BackgroundBronchopulmonary dysplasia (BPD) is a major problem for extremely preterm infants. Glucocorticoids effectively treat BPD; however, they have many side effects. Compound A (Cpd A) is a nonsteroidal Selective Glucocorticoid Receptor Modulator (SEGRM) that acts as a glucocorticoid receptor ligand without inducing the expression of glucocorticoid-response element-driven genes. Cpd A reportedly has anti-inflammatory properties with fewer side effects than glucocorticoids. MethodsUsing a bleomycin (Bleo)-induced BPD model, we evaluated the therapeutic effects of Cpd A. 0-day-old Sprague-Dawley rats were administered Bleo for 10 days and treated with dexamethasone (Dex) or Cpd A from day 0 to 13. We evaluated lung pathology by histology and the mRNA levels of interleukin (IL)-1{beta}, transforming growth factor (TGF)-{beta}1 and chemokines, CXCL1 and CCL2. ResultsBleo-treated mice had lungs with impaired alveolarization. Dex and Cpd A treatments improved the alveolar structure, attenuating the lung injury. Bleo-exposed lungs had increased inflammatory cells recruitment and inflammatory mediator mRNA levels. Cpd A treatment reduced inflammatory cells infiltration and CXCL1, CCL2 and TGF-{beta}1 expression. ConclusionCpd A improved lung inflammation and alveolar maturation arrest, and restored histological and biochemical changes in a model of BPD. SEGRMs, including Cpd A, are promising candidates for the therapy of BPD. Impact Statement{circ} What is the key message of your article? Compound A decreased lung inflammation and improved lung morphometric changes in Bleomycin-exposed lungs. {circ}What does it add to the existing literature? Compound A has anti-inflammatory effects in an experimental model of BPD. {circ}What is the impact? SEGRMs, including Cpd A, may be promising candidates for the therapy of BPD.

pathology↗

bioRxiv2021

Coordination between growth and stress responses by DELLA in the liverwort Marchantia polymorpha

Plant survival depends on the optimal use of resources under variable environmental conditions. Among the mechanisms that mediate the balance between growth, differentiation and stress responses, the regulation of transcriptional activity by DELLA proteins stands out. In angiosperms, DELLA accumulation promotes defense against biotic and abiotic stress and represses cell division and expansion, while loss of DELLA function is associated with increased plant size and sensitivity towards stress1. Given that DELLA protein stability is dependent on gibberellin (GA) levels2, and GA metabolism is influenced by the environment3, this pathway is proposed to relay environmental information to the transcriptional programs that regulate growth and stress responses in angiosperms4,5. However, DELLA genes are also found in bryophytes, whereas canonical GA receptors appeared only in vascular plants6-10. Thus, it is not clear whether these regulatory functions of DELLA predated or emerged with typical GA signaling. Here we show that, as in vascular plants, the only DELLA in the liverwort Marchantia polymorpha also participates in the regulation of growth and key developmental processes, and promotes the tolerance towards oxidative stress. Moreover, part of these effects is likely caused by the conserved physical interaction with the MpPIF transcription factor. Therefore, we suggest that the role in the coordination of growth and stress responses was already encoded in DELLA from the common ancestor of land plants, and the importance of this function is justified by its conservation over the past 450 M years.

plant biology↗

bioRxiv2020

Deep evolutionary origin of gamete-directed zygote activation by KNOX/BELL transcription factors in green plants

KNOX and BELL transcription factors regulate distinct steps of diploid development in the green lineages. In the green alga Chlamydomonas reinhardtii, KNOX and BELL proteins are inherited by gametes of the opposite mating types, and heterodimerize in zygotes to activate diploid development. By contrast, in land plants such as Physcomitrella and Arabidopsis, KNOX and BELL proteins function in meristem maintenance and organogenesis during the later stages of diploid development. However, whether the contrasting functions of KNOX and BELL were acquired independently in algae and land plants is currently unknown. Here we show that in the basal land plant species Marchantia polymorpha, gamete-expressed KNOX and BELL are required to initiate zygotic development by promoting nuclear fusion in a manner strikingly similar to that of C. reinhardtii. Our results indicate that zygote activation is the ancestral role of KNOX/BELL transcription factors, which shifted toward meristem maintenance as land plants evolved.

developmental biology↗

bioRxiv2019

Chromatin organization in early land plants reveals an ancestral association between H3K27me3, transposons, and constitutive heterochromatin

Genome packaging by nucleosomes is a hallmark of eukaryotes. Histones and the pathways that deposit, remove, and read histone modifications are deeply conserved. Yet, we lack information regarding chromatin landscapes in extant representatives of ancestors of the main groups of eukaryotes and our knowledge of the evolution of chromatin related processes is limited. We used the bryophyte Marchantia polymorpha, which diverged from vascular plants 400 Mya, to obtain a whole chromosome genome assembly and explore the chromatin landscape and three-dimensional organization of the genome of early land plants. Based on genomic profiles of ten chromatin marks, we conclude that the relationship between active marks and gene expression is conserved across land plants. In contrast, we observed distinctive features of transposons and repeats in Marchantia compared with flowering plants. Silenced transposons and repeats did not accumulate around centromeres, and a significant proportion of transposons were marked by H3K27me3, which is otherwise dedicated to the transcriptional repression of protein coding genes in flowering plants. Chromatin compartmentalization analyses of Hi-C data revealed that chromatin regions belonging to repressed heterochromatin were densely decorated with H3K27me3 but not H3K9 or DNA methylation as reported in flowering plants. We conclude that in early plants, H3K27me3 played an essential role in heterochromatin function, suggesting an ancestral role of this mark in transposon silencing.

molecular biology↗

bioRxiv2018

Loss of CG methylation in Marchantia polymorpha causes disorganization of cell division and reveals unique DNA methylation regulatory mechanisms of non-CG methylation.

DNA methylation is an epigenetic mark that ensures silencing of transposable elements (TEs) and affects gene expression in many organisms. The function of different DNA methylation regulatory pathways has been largely characterized in the model plant Arabidopsis thaliana. However, far less is known about DNA methylation regulation and functions in basal land plants. Here we focus on the liverwort Marchantia polymorpha, an emerging model species that represents a basal lineage of land plants. We identified MpMET, the M. polymorpha orthologue of the METHYLTRANSFERASE 1 (MET1) gene required for maintenance of methylation at CG sites in angiosperms. We generated Mpmet mutants using the CRISPR/Cas9 system, which showed a significant loss of CG methylation and severe morphological changes and developmental defects. The mutants developed many adventitious shoot-like structures, suggesting that MpMET is required for maintaining differentiated cellular identities in the gametophyte. Numerous TEs were up-regulated, even though non-CG methylation was highly increased at TEs in the Mpmet mutants. Closer inspection of CHG methylation revealed features unique to M. polymorpha. Methylation of CCG sites in M. polymorpha does not depend on MET1, unlike in A. thaliana and Physcomitrella patens. Furthermore, unlike A. thaliana, M. polymorpha shows higher methylation level at CAG sites than at other CHG contexts and CAG/CTG sites are mostly methylated asymmetrically. Interestingly, CAG and CTG methylation reached comparable levels and symmetry upon loss of CG methylation. Our results highlight the diversity of non-CG methylation regulatory mechanisms in plants.

plant biology↗