Biology subjects

Ono, N.

Publications and source records attributed to Ono, N..

14 recordsLinked to original sources

bioRxiv2026

Rice blast fungus hijacks a rice RALF peptide to initiate infection

Plant-derived peptides regulate immunity and host-microbe interactions, but whether fungal pathogens exploit endogenous plant peptides for infection-site selection remains largely unknown. Rapid alkalinization factors (RALFs) are a family of plant peptide hormones that contribute to plant development, reproduction, stress responses, and cell-wall organization. Here, we show that OsRALF7, which is an immune-activating peptide in rice (Oryza sativa), is co-opted by the rice blast fungus Magnaporthe oryzae as a host-derived cue for appressorium formation, specialized infection structures required for host penetration. While synthetic OsRALF7 peptide induced defense responses in rice suspension cells, the same peptide induced appressorium formation in M. oryzae. OsRALF7-induced appressorium formation was associated with activation of the cAMP/PKA and Pmk1 MAPK pathways and required a hydrophobic surface. M. oryzae inoculated onto Osralf7 knockout plants formed fewer appressoria, and the positioning of these appressoria relative to the boundaries between two adjacent plant epidermal cells was altered. These findings suggest that OsRALF7 provides positional information for infection initiation for M. oryzae. OsRALF7 localized to the plasma membrane and cell wall in rice, and its appressorium-inducing activity required a conserved YISY motif and cysteine residues. This activity was not conserved in Colletotrichum higginsianum, as RALF23 from Arabidopsis thaliana did not induce appressorium formation but instead showed antifungal activity. Together, these findings uncover a dual function of endogenous plant immune-modulating RALF peptides at the plant-pathogen interface, where they can be exploited by M. oryzae as a host-derived cue for infection initiation while also retaining antifungal activity against other fungal species.

plant biology↗

bioRxiv2024

Control of alveolar bone development, homeostasis, and socket healing by salt inducible kinases

Alveolar bone supports and anchors teeth. The parathyroid hormone-related protein (PTHrP) pathway plays a key role in alveolar bone biology. Salt inducible kinases (SIKs) are important downstream regulators of PTH/PTHrP signaling in the appendicular skeleton where SIK inhibition increases bone formation and trabecular bone mass. However, the function of these kinases in alveolar bone remains unknown. Here, we report a critical role for SIK2/SIK3 in alveolar bone development, homeostasis, and socket healing after tooth extraction. Inducible SIK2/SIK3 deletion led to dramatic alveolar bone defects without changes in tooth eruption. Ablating these kinases impairs alveolar bone formation due to disrupted osteoblast maturation, a finding associated with ectopic periostin expression by fibrous cells in regions of absent alveolar bone at steady state and following molar extraction. Distinct phenotypic consequences of SIK2/SIK3 deletion in appendicular versus craniofacial bones prompted us to identify a specific transcriptomic signature in alveolar versus long bone osteoblasts. Thus, SIK2/SIK3 deletion illuminates a key role for these kinases in alveolar bone biology and highlights the emerging concept that different osteoblast subsets utilize unique genetic programs. Summary statementSIK2/SIK3 deletion in alveolar bone reduces bone formation and mass by impairing osteoblast maturation, unlike in long bones, where it increases bone formation and mass.

developmental biology↗

bioRxiv2024

Soil nutrition-dependent dynamics of the root-associated microbiome in paddy rice

O_LIPlants accommodate diverse microbial communities (microbiomes), which can change dynamically during plant adaptation to varying environmental conditions. However, the direction of these changes and the underlying mechanisms driving them, particularly in crops adapting to the field conditions, remain poorly understood. C_LIO_LIWe investigate the root-associated microbiome of rice (Oryza sativa L.) using 16S rRNA gene amplicon and metagenome sequencing, across four consecutive cultivation seasons in a high-yield, non-fertilized, and pesticide-free paddy field, compared to a neighboring fertilized and pesticide-treated field. C_LIO_LIOur findings reveal that root microbial community shifts and diverges based on soil fertilization status and plant developmental stages. Notably, nitrogen-fixing bacteria such as Telmatospirillum, Bradyrhizobium and Rhizomicrobium were over-represented in rice grown in the non-fertilized field, implying that the assembly of these microbes supports rice adaptation to nutrient-deficient environments. C_LIO_LIA machine learning model trained on the microbiome data successfully predicted soil fertilization status, highlighting the potential of root microbiome analysis in forecasting soil nutrition levels. Additionally, we observed significant changes in the root microbiome of ccamk mutants, which lack a master regulator of mycorrhizal symbiosis, under laboratory conditions but not in the field, suggesting a condition-dependent role for CCaMK in establishing microbiomes in paddy rice. C_LI

plant biology↗

bioRxiv2024

CytoSignal Detects Locations and Dynamics of Ligand-Receptor Signaling at Cellular Resolution from Spatial Transcriptomic Data

Nearby cells within tissues communicate through ligand-receptor signaling interactions. Emerging spatial transcriptomic technologies provide a tremendous opportunity to systematically detect ligand-receptor signaling, but no method operates at cellular resolution in the spatial context. We developed CytoSignal to infer the locations and dynamics of cell-cell communication at cellular resolution from spatial transcriptomic data. CytoSignal is based on the simple insight that signaling is a protein-protein interaction that occurs at a specific tissue location when ligand and receptor are expressed in close spatial proximity. Our cellular-resolution, spatially-resolved signaling scores allow several novel types of analyses: we identify spatial gradients in signaling strength; separately quantify the locations of contact-dependent and diffusible interactions; and detect signaling-associated differentially expressed genes. Additionally, we can predict the temporal dynamics of a signaling interaction at each spatial location. CytoSignal is compatible with nearly every kind of spatial transcriptomic technology including FISH-based protocols and spot-based protocols without deconvolution. We experimentally validate our results in situ by proximity ligation assay, confirming that CytoSignal scores closely match the tissue locations of ligand-receptor protein-protein interactions. Our work addresses the fields current need for a robust and scalable tool to detect cell-cell signaling interactions and their dynamics at cellular resolution from spatial transcriptomic data.

bioinformatics↗

bioRxiv2023

CytoSimplex: Visualizing Single-cell Fates and Transitions on a Simplex

SummaryCells differentiate to their final fates along unique trajectories, often involving multi-potent progenitors that can produce multiple terminally differentiated cell types. Recent developments in single-cell transcriptomic and epigenomic measurement provide tremendous opportunities for mapping these trajectories. The visualization of single-cell data often relies on dimension reduction methods such as UMAP to simplify high-dimensional single-cell data down into an understandable two-dimensional (2D) form. However, these visualization methods can be misleading and often do not effectively represent the direction of cell differentiation. To address these limitations, we developed a new approach that places each cell from a single-cell dataset within a simplex whose vertices correspond to terminally differentiated cell types. Our approach can quantify and visualize current cell fate commitment and future cell potential. We developed CytoSimplex, a standalone open-source package implemented in R and Python that provides simple and intuitive visualizations of cell differentiation in 2D ternary and three-dimensional (3D) quaternary plots. We believe that CytoSimplex can help researchers gain a better understanding of cell type transitions in specific tissues and characterize developmental processes. Availability and implementationThe R version of CytoSimplex is available on Github at https://github.com/welch-lab/CytoSimplex. The Python version of CytoSimplex is available on Github at https://github.com/welch-lab/pyCytoSimplex.

bioinformatics↗

bioRxiv2023

Growth plate resting zone chondrocytes acquire transient clonal competency upon Hedgehog activation and efficiently transform into trabecular bone osteoblasts

The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-indian hedgehog (Ihh) feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP+ resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we utilized a tamoxifen-inducible PTHrP-creER line with Patched-1 (Ptch1) floxed and tdTomato reporter alleles to specifically activate Hedgehog signaling in PTHrP+ resting chondrocytes and trace the fate of their descendants. Hedgehog-activated PTHrP+ chondrocytes formed large concentric clonally expanded cell populations within the resting zone ( patched roses) and generated significantly wider columns of chondrocytes, resulting in hyperplasia of the growth plate. Interestingly, Hedgehog-activated PTHrP+ cell-descendants migrated away from the growth plate and eventually transformed into trabecular osteoblasts in the diaphyseal marrow space in the long term. Therefore, Hedgehog activation drives resting zone chondrocytes into transit-amplifying states as proliferating chondrocytes and eventually converts these cells into osteoblasts, unraveling a novel Hedgehog-mediated mechanism that facilitates osteogenic cell fates of PTHrP+ skeletal stem cells.

developmental biology↗

bioRxiv2023

Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used MERFISH to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations; charted their spatial organization; and revealed their polarization or recruitment in inflammation. We found a staged progression of inflammation-associated tissue neighborhoods defined, in part, by multiple inflammation-associated fibroblasts, with unique expression profiles, spatial localization, cell-cell interactions, and healthy fibroblast origins. Similar signatures in ulcerative colitis suggest conserved human processes. Broadly, we provide a framework for understanding inflammation-induced remodeling in the gut and other tissues.

immunology↗

bioRxiv2022

Control of Craniofacial Development by the Collagen Receptor, Discoidin Domain Receptor 2

Development of the craniofacial skeleton requires interactions between progenitor cells and the collagen-rich extracellular matrix (ECM). The mediators of these interactions are not well-defined. Mutations in discoidin domain receptor 2 (DDR2), a non-integrin collagen receptor, are associated with craniofacial abnormalities, such as midface hypoplasia and open fontanels. However, the exact role of DDR2 in craniofacial morphogenesis is not known. As will be shown, Ddr2-deficient mice exhibit defects in craniofacial bones including impaired calvarial growth and frontal suture formation, cranial base hypoplasia due to aberrant chondrogenesis and delayed ossification at growth plate synchondroses. As established by localization and lineage tracing studies, Ddr2 is expressed in progenitor cell-enriched craniofacial regions including sutures and synchondrosis resting zone cartilage, overlapping with Gli1+ cells, and contributing to chondrogenic and osteogenic lineages during skull growth. Tissue-specific knockouts further established the requirement for Ddr2 in Gli1+ skeletal progenitors and chondrocytes and suggest important functions in chondrocyte proliferation and orientation as well as ECM organization. These studies establish a cellular basis for regulation of craniofacial morphogenesis by this understudied collagen receptor.

developmental biology↗

bioRxiv2021

Integrated Metabolomics to Reveal the Impacts of Common Antibiotics based on Drug Resistance Prediction of Gut Microbiota

Due to the close interaction between the host and the gut microbiota, the alterations in gut microbiota metabolism may therefore contribute to various diseases. How to use antibiotics more wisely in clinical practice is a promising task in the field of pathophysiology related to gut microbiota. The hope fueling this research is that the alteration of gut microbial communities are paralleled by their capacity on metabolomic from the combined perspective of microbiome and metabolomics. In order to reveal the impacts of antibiotics on microbiota-associated host metabolomic phenotypes, a feasible methodology should be well developed to assess the pervasive effects of antibiotics on the population structure of gut microbial communities. Our attempt starts from predicting specific resistance phenotypes of the individuals in isolation from the rest of the gut microbiota community, according to their resistant genotypes. Once resistance phenotypes of microbiome is determined, we integrated metabolomics with machine learning by applying various analysis algorithms to explore the relationship between the predicted resistance and metabolites, including what the microbial community is after medication, which microbes produce metabolites, and how these metabolites enrich.

bioinformatics↗

bioRxiv2020

Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment

Chondrocytes in the resting zone of the postnatal growth plate are characterized by slow cell cycle progression, and encompass a population of parathyroid hormone-related protein (PTHrP)-expressing skeletal stem cells that contribute to the formation of columnar chondrocytes. However, how these chondrocytes are maintained in the resting zone remains undefined. We undertook a genetic pulse-chase approach to isolate slow cycling, label-retaining chondrocytes (LRCs) from the growth plate using a chondrocyte-specific doxycycline-controllable Tet-Off system regulating expression of histone 2B-linked GFP. Comparative RNA-seq analysis identified significant enrichment of inhibitors and activators for Wnt/{beta}-catenin signaling in LRCs and non-LRCs, respectively. Activation of Wnt/{beta}-catenin signaling in PTHrP+ resting chondrocytes using Pthrp-creER and Apc-floxed allele impaired their ability to form columnar chondrocytes. Therefore, slow-cycling chondrocytes are maintained in a canonical Wnt-inhibitory environment within the resting zone, unraveling a novel mechanism regulating maintenance and differentiation of PTHrP+ skeletal stem cells of the postnatal growth plate.

developmental biology↗

bioRxiv2020

Notch effector Hes1 marks an early perichondrial population of skeletal progenitor cells at the onset of endochondral bone development

The perichondrium, a fibrous tissue surrounding the fetal cartilage, is an essential component of developing endochondral bones that provides a source of skeletal progenitor cells. However, perichondrial cells remain poorly characterized due to lack of knowledge on their cellular diversity and subset-specific mouse genetics tools. Single cell RNA-seq analyses reveal a contiguous nature of the fetal chondrocyte-perichondrial cell lineage that shares an overlapping set of marker genes. Subsequent cell-lineage analyses using multiple creER lines active in fetal perichondrial cells - Hes1-creER, Dlx5-creER - and chondrocytes - Fgfr3-creER - illustrate their distinctive contribution to endochondral bone development; postnatally, these cells contribute to the functionally distinct bone marrow stromal compartments. Particularly, Notch effector Hes1-creER marks an early skeletal progenitor cell population in the primordium that robustly populates multiple skeletal compartments. These findings support the concept that perichondrial cells participate in endochondral bone development through a distinct route, by providing a complementary source of skeletal progenitor cells.

developmental biology↗

bioRxiv2019

The Feasibility of Predicting Impending Malignant Ventricular Arrhythmias on the basis of Signal Complexity of Heartbeat Intervals

Malignant ventricular arrhythmias (MAs), such as ventricular tachycardia (VT) that presages cardiac arrest, present the highest hurdle for the healthcare community to overcome. Given that MAs occur unpredictably and lead to emergencies, convenient tracking devices, e.g. photoplethysmogram (PPG), that could predict MAs would be irreplaceably valuable. Since the use of heartbeat intervals (HbI) to predict the occurrence of arrhythmias is becoming more feasible, a further attempt to establish a new convenient approach for predicting impending MAs with HbI is worth trying. Assuming that intrinsic characteristics of MAs (VT and ventricular fibrillation: VF) can be revealed by a suitable approach on the basis of signal complexity, we propose an approach that first expresses the physiological status of the heart by HbI; then delineates the patterns of HbI by a new complexity metric (refined composite multi-scale entropy: RCMsEn); and finally trains a nonlinear machine learning model (random forest: RF) to learn the specific patterns of MAs so as to differentiate them from the normal sinus heart rhythm(N) and other prevalent arrhythmias (atrial fibrillation: AF, and premature ventricular contraction: V). For calculating entropy values and predicting MAs as early as possible (which is the aim of this study), two specifications are of interest: the minimal length of HbI needed to delineate the MAs patterns sufficiently (lenmin), and the maximum time length at which our model can predict impending MAs (timemax). We compared the RF model with support vector machine (SVM) models based on linear and Gaussian kernels. Results show that the RF model performs the best, reaching a 99.24% recall and a 99.87% precision for a HbI of 500 heartbeats (the lenmin) 374 seconds (the timemax) preceding the occurrence of MAs. The HbI samples in this study were extracted from an electrocardiograph (ECG). However, given the subtle difference (0.1 ms typically) between the R-R interval of ECG and the P-P interval of PPG, this approach could be extended to HbI acquired by the PPG sensor and thus should be of substantial theoretical and practical significance in cardiac arrest prevention.

bioinformatics↗

bioRxiv2019

The feasibility of atrial and ventricular arrhythmias recognition using metrics of signal complexity for heartbeat intervals

It is well known that the cardiac system is controlled by the complex nonlinear self-regulation and the heartbeat variability (HRV) is an independent indicator of the autonomic regulation. With the assumption that intrinsic differences of atrial fibrillation (A) and ventricular ectopic arrhythmias (V) can be unveiled by a proper approach based on of signal complexity, we examine the feasibility of detecting these arrhythmias of different pathological origins using metrics of complexity for heartbeat intervals (HRI). Specifically, the normal sinus rhythm (N), the A type and the V type are used as the targeted types of heartbeat. By extracting the entropy-based features from HRI of different lengths, i.e., from 300 heartbeats to 1000 heartbeats, we examined the distinguishability of these 3 types of heartbeat. By applying the features to the random forest model, the HRI signal of 600-heartbeat-length can be used to detect the A and V completely, i.e., with 100% of type-wise recall and precision. What is more, this approach is sensitive to the existence of the corresponding arrhythmias. The results substantiate our assumption about the intrinsic difference of the A and V type. A further investigation applying this approach to a wider spectrum and a finer stratification of arrhythmias/ cardiac diseases and may lead to the systematic understanding in the context of complexity and better insight for its practical use for wearable/unconstrained monitors.

physiology↗

bioRxiv2019

Social tolerance in Octopus laqueus - a maximal entropy model

Octopus laqueus is a small tropical octopus found in Okinawa, Japan and the greater Indo-Pacific. Octopus are often viewed as solitary animals but O. laqueus live in close proximity in the wild, and will potentially encounter one another on a regular basis, raising the possibility of sociality in the species. To test for social tolerance and social repulsion in O. laqueus, animals were kept in communal tanks, and the number of dens and sex composition was varied per tank, with a set mixture of sizes and with den occupancy tracked per individual. We found that O. laqueus will socially tolerate other individuals by sharing tanks and dens, including several animals in contact and sharing a den under den-limited conditions, and with typically no loss to cannibalism or escape. However, animals also exhibit significant levels of social repulsion, and individuals often chose a solitary den when given the option. The patterns of den occupancy are observed to be consistent with a maximum entropy model. Overall, the preference to have a den is stronger than the preference to be solitary in O. laqueus, and the animals are socially tolerant of others in the tank and in a den or shelter, a first for octopuses outside mating. The relaxed disposition and social tolerance of O. laqueus make it a promising species to work with in lab, and for development into a genetic model for social behavior in octopuses.

animal behavior and cognition↗