Biology subjects

Kono, M.

Publications and source records attributed to Kono, M..

12 recordsLinked to original sources

bioRxiv2026

From photoprotection to growth: shifts in high-light acclimation strategies associated with molecular evolutionary rates in duckweeds

Molecular evolutionary rates vary widely among lineages, yet the biological processes generating this variation remain poorly understood. In plants, which lack an early-segregated germline, growth- and environment-dependent physiology could itself influence mutation accumulation and, ultimately, substitution rates. Here we examine this possibility in duckweeds (Araceae, Lemnoideae), whose closely related lineages differ severalfold in sequence divergence. Nonsynonymous and synonymous divergence scaled proportionally across all six lineages examined, indicating that this heterogeneity does not reflect differences in selective constraint and instead points to variation in mutation rate. Lineages without prominent anthocyanin accumulation occupied lower latitudes and, under high light, sustained higher relative growth rates and higher photosynthetic efficiency. Comparing the early-diverging, anthocyanin-accumulating Spirodela polyrhiza with the late-diverging, anthocyanin-free Wolffia australiana revealed contrasting acclimation strategies: S. polyrhiza preferentially induced photoprotective pathways, including anthocyanin biosynthesis and non-photochemical quenching, whereas W. australiana instead expanded mitochondrial oxidative phosphorylation together with the cytosolic translational machinery, and broadly remodeled primary metabolism. Duckweed lineages therefore differ in how they balance photoprotection against photochemical energy use and downstream metabolic capacity, a divergence that may be associated with their lineage-specific molecular evolutionary rates.

evolutionary biology↗

bioRxiv2026

CATaN maps gene regulatory programs that shape genetic risk across complex diseases

Causal variants of complex traits are enriched at transcription factor (TF) binding sites and are thought to contribute to pathology by disrupting TF activity and thereby causing transcriptome dysregulation. However, existing approaches typically address TF-mediated gene regulatory networks (TF-GRNs) and transcriptomes separately, and methods that jointly leverage both to systematically assess disease heritability remain limited. We aimed to develop a framework that jointly leverages TF-GRNs and transcriptomes to assess disease heritability. Here, we constructed a matrix encoding TF-GRNs and developed an unsupervised analytical pipeline, Canonical correlation Analysis of Transcriptome and TF-gene regulatory Networks (CATaN). CATaN applies canonical correlation analysis (CCA) to extract canonical correlation (CC) components, i.e., shared variation components between transcriptomes and TF-GRNs, and converts them into genome-wide functional annotation scores connected to stratified LD score regression (S-LDSC) for heritability analysis. We applied CATaN to eight datasets, including 19,198 bulk samples and 611,772 single cells from human and mouse sources, identifying 588 CC components that are significantly enriched for SNP heritability across 69 complex traits. Notably, functional annotation tracks based on these TF-GRNs are distinct from transcriptome signatures prioritized by LDSC-SEG, with greater heritability enrichment for a subset of traits. Finally, we suggest that CATaN may help prioritize candidate causal variants for experimental fine-mapping using genome editing. Together, integrating TF-GRNs with transcriptomes reveals disease-relevant regulatory programs that are not fully captured by transcriptome-based analyses alone.

genetics↗

bioRxiv2025

Cellular and molecular fine mapping pinpoints new immunopathology of lupus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with an unknown etiology. To pinpoint new disease-relevant cell states and their molecular profiles, we performed an in-depth investigation of multimodal single-cell datasets comprising [~]2.1 million peripheral blood mononuclear cells from 346 donors. By resolving 123 fine-grained cell states across 27 cell types, we identified previously uncharacterized populations distinctively associated with clinical severity and treatment status, including GZMK+GZMH+HLA-DR+ effector memory CD8+ T cells (double-positive [DP] EMCD8) and FOXO1+ARHGAP15+ T cells. Through extensive statistical frameworks and multimodal approaches, we delineated their aberrant immune signaling networks, transcriptional regulators, key surface proteins, T cell receptor repertoires, and genetic/epigenetic landscapes, underscoring them as candidate drivers of SLE immunopathology. These findings provide new insights into therapeutic target discovery in SLE.

immunology↗

bioRxiv2025

1-Deoxysphingolipids Require Very-Long-Chain Ceramide Synthesis to Induce ER Stress and Neurotoxicity

Sphingolipids play key roles in cellular systems both as membrane components and as signaling molecules. Their biosynthesis, which occurs in the endoplasmic reticulum (ER), begins with the condensation of an amino acid, typically serine, and a fatty acyl-CoA. Under certain pathological conditions, alanine can be substituted for serine in the condensation reaction, producing 1-deoxysphingolipids, which lack the 1-hydroxyl group on the sphingoid base. Unlike typical sphingolipids, 1-deoxysphingolipids are unable to accept a head group modification, which alters their metabolic processing and prevents their canonical degradation. The accumulation of these "headless" 1-deoxysphingolipids causes neurotoxicity in various neurological and metabolic disorders. Here, we conducted a genome-wide CRISPR-Cas9 screen to identify pathways leading to 1-deoxysphinganine-induced toxicity in SH-SY5Y cells, a model used to study neurotoxic responses. Our top genetic hits highlighted the pathway involved in synthesizing ceramides with very-long-chain fatty acids (C22-C26). Using CRISPR-Cas9-modified SH-SY5Y cells with loss-of-function (LOF) mutations in the TECR or CERS2 genes--both critical for producing very-long-chain ceramides--we validated that this pathway was essential for 1-deoxysphinganine-mediated toxicity. Furthermore, we demonstrated that the ceramide synthesis pathway is required for 1-deoxysphinganine to trigger ER stress, as evidenced by significantly increased expression of the unfolded protein response in WT, but not TECR or CERS2 LOF mutant, SH-SY5Y cells exposed to 1-deoxysphinganine. Collectively, these findings identify a specific metabolic pathway for 1-deoxysphinganine leading to very-long-chain 1-deoxyceramide production that culminates in ER stress and toxicity. The findings highlight potential therapeutic targets for neuropathological diseases caused by 1-deoxysphingolipid accumulation.

biochemistry↗

bioRxiv2025

Cyt b6/f Complex Fine-Tunes PSI Stability and Photosynthetic Capacity Under Fluctuating Light

Plants encounter dynamic light fluctuations in natural habitats, requiring robust mechanisms to protect Photosystem I (PSI) against photoinhibition. The cytochrome (Cyt) b6/f complex plays a pivotal role in regulating electron flow and ensuring PSI stability under fluctuating light. However, its precise role in balancing PSI protection and photosynthetic capacity remains unclear. In this study, transgenic tobacco (Nicotiana tabacum L. W38) with reduced Cyt b6/f content was used to examine PSI tolerance to photoinhibition and photosynthetic performance under fluctuating light. Notably, the reduced Cyt b6/f content conferred significant protection of PSI against photoinhibition induced by fluctuating light, albeit at the expense of the electron transport capacity. Remarkably, PSI stability was maintained even under extreme fluctuating light conditions in the plants with lowest Cyt b6/f contents, highlighting a trade-off between photoprotection and photosynthetic capacity. These findings reveal that a reduction in Cyt b6/f content enhances PSI protection while adjusting electron transport capacity, making plants more adaptable in environments dominated by low light and transient sunflecks. This study provides new insights into the adaptive strategies of plants under dynamic light environments and underscores the potential of targeting Cyt b6/f for enhancing crop tolerance to fluctuating light conditions.

plant biology↗

bioRxiv2024

Cancer vaccine attenuates carcinogen induced head and neck cancer with impaired early T cell response

Effective T cell immunotherapy requires understanding antigen-specific T cell development during tumorigenesis and immune surveillance. Here, we aimed to examine the dynamics of antigen-specific T cells from tumor initiation through progression in a tobacco carcinogen mimetic, 4-nitroquinoline-1-oxide (4NQO)-induced head and neck carcinogenesis model utilizing genetically engineered K5CreERT/+/ROSAOVA-GFP/p53fl/fl (KOG) mice. Our findings showed that early ovalbumin (OVA) expression via direct lingual tamoxifen (T) did not impact cancer development and survival, by comparing mice with tongue epithelium expressing OVA (KOG/T/OVA+) to those without OVA (KOG/T/OVA-) controlled by doxycycline. This equivalent tumor growth cannot be attributed to the loss of OVA expression. Intriguingly, although OVA-specific T cells were initially generated in tumor-draining lymph nodes (TDLN), they became undetectable 3 weeks after tamoxifen injection. Moreover, therapeutic anti-PD-1 was unable to restore OVA-specific T cells in TDLN and did not yield anti-tumor activity. Remarkably, OVA synthetic long peptide (SLP) vaccine induced OVA-specific T cells in KOG/T/OVA+ mice, and the combination of SLP vaccine and anti-PD-1 significantly reduced tongue tumor burden and prolonged survival. This study highlights the role of impaired endogenous antigen-specific T cell responses in immune resistance in head and neck cancer and the potential of cancer vaccines to improve outcomes.

cancer biology↗

bioRxiv2024

Excitation Spillover from PSII to PSI Measured in Leaves at 77K

Heterogeneous distribution of PSI and PSII in thick grana in shade chloroplasts is argued to hinder spillover of chlorophyll excitations from PSII to PSI. To examine this dogma, we measured fluorescence induction at 77K at 690 nm (PSII) and 760 nm (mainly PSI) in the leaf discs of Spinacia oleracea, Cucumis sativus and shade tolerant Alocasia odora, grown at high and low light, and quantified their spillover capacities. PSI fluorescence (FI) consists of the intrinsic PSI fluorescence (FI) and fluorescence caused by excitations spilt over from PSII (FI{beta}). When FI and FII parameters between State 1 and State 2, induced by weak far-red and blue light, were compared, PSII maximum fluorescence (FIIm) and FI{beta} were greater, and FI was smaller in State 1 and thereby the spillover ratio, FI{beta}/(FI +FI{beta}) or FI{beta}/FIm, was greater in State 1. Since the leftover FIIm was found to be about 10% of total Fm at 760 nm, all the data were corrected. Even after the correction, the spillover ratio in FIm in State 1 ranged from 21 to 32%, and the spillover ratios were comparable irrespective of growth light conditions. Although extensive grana in low light grown plants would suggest that PSII and PSI are too separated for spillover, in A. odora chloroplasts, the ratio of non-appressed thylakoid membranes/total thylakoid membranes was little affected by growth light and more than 40%. Abundant non-appressed thylakoids would contribute to efficient spillover.

plant biology↗

bioRxiv2023

The third symbiotic partner of the volcano lichen Cladonia vulcani Savicz drove adaptation to an extreme environment.

Chemosynthetic symbioses between sulfur-oxidizing bacteria and aquatic eukaryotes have been discovered globally in sulfide-rich environments, notably deep-sea hydrothermal vents, cold seeps, and sulfidic cave systems. However, to the best of our knowledge, such chemosymbiotic lifestyles have not been reported from terrestrial eukaryotes. Here we report that the volcano lichen Cladonia vulcani Savicz ubiquitously associates with a single bacterial species that could potentially use hydrogen sulfide as a source of energy. We identified sequences of the bacterium in all 27 samples collected from five geothermal areas across Japan with cellular abundance comparable to the fungal partner. The assembled bacterial genome contained genes involved in sulfur oxidation. The stable association with a potential sulfur-oxidizer is likely to represent an obligate tripartite symbiotic system consisting of fungal, algal, and bacterial partners that has enabled adaptation to the extreme environment.

evolutionary biology↗

bioRxiv2021

Large differences in carbohydrate degradation and transport potential in the genomes of lichen fungal symbionts

Lichen symbioses are generally thought to be stabilized by the transfer of fixed carbon compounds from a photosynthesizing unicellular symbiont to a fungus. In other fungal symbioses, carbohydrate subsidies correlate with genomic reductions in the number of genes for plant cell wall-degrading enzymes (PCWDEs), but whether this is the case with lichen fungal symbionts (LFSs) is unknown. We predicted genes encoding carbohydrate-active enzymes (CAZymes) and sugar transporters in 17 existing and 29 newly sequenced genomes from across the class Lecanoromycetes, the largest extant clade of LFSs. Despite possessing lower mean numbers of PCWDE genes compared to non-symbiont Ascomycota, all LFS genomes possessed a robust suite of predicted PCWDEs. The largest CAZyme gene numbers, on par with model species such as Penicillium, were retained in genomes from the subclass Ostropomycetidae, which are found in crust lichens with highly specific ecologies. The lowest numbers were in the subclass Lecanoromycetidae, which are symbionts of many generalist macrolichens. Our results suggest that association with phototroph symbionts does not in itself result in functional loss of PCWDEs and that PCWDE losses may have been driven by adaptive processes within the evolution of specific LFS lineages. The inferred capability of some LFSs to access a wide range of carbohydrates suggests that some lichen symbioses may augment fixed CO2 with carbon from external sources. SignificanceLichen symbioses are considered self-contained autotrophic systems in which the total carbon economy is the sum of phototroph-fixed CO2, supplied to a fungus as sugars. In other fungal-plant symbioses, such as mycorrhizae, plant-derived sugar subsidies are associated with loss of plant cell wall-degrading enzymes (PCWDEs). We compared PCWDE inventories in 46 genomes from the largest group of lichen fungal symbionts (LFSs) with non-symbionts from across Ascomycota. We found that despite lower overall gene numbers, all LFSs retain PCWDEs, and some possess gene numbers and functional diversity on par with non-symbionts. Our results suggest that association with a phototroph does not necessarily result in PCWDE loss, and some lichens may obtain carbon from sources other than CO2 fixation.

genomics↗

bioRxiv2019

Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta

Despite the medical importance of G protein-coupled receptors (GPCRs), in vivo cellular heterogeneity of GPCR signaling and downstream transcriptional responses are not understood. We report the comprehensive characterization of transcriptomes (bulk and single-cell) and chromatin domains regulated by sphingosine 1-phosphate receptor-1 (S1PR1) in adult mouse aortic endothelial cells. First, S1PR1 regulates NFkB and nuclear glucocorticoid receptor pathways to suppress inflammation-related mRNAs. Second, spatially distinct S1PR1 signaling in the aorta is associated with heterogenous endothelial cell (EC) subtypes. For example, a transcriptomically distinct arterial EC population at vascular branch points (aEC1) exhibits ligand- independent S1PR1/{beta}-arrestin coupling. In contrast, circulatory S1P-dependent S1PR1/{beta}-arrestin coupling was observed in non-branch point aEC2 cells that exhibit an inflammatory signature. Moreover, an adventitial lymphatic EC (LEC) population shows suppression of lymphangiogenic and inflammation-related transcripts in a S1P/S1PR1-dependent manner. These insights add resolution to existing concepts of GPCR signaling and S1P biology.

molecular biology↗

bioRxiv2019

DLDG1, the Arabidopsis Homolog of the Cyanobacterial H+-Extrusion Protein, Regulates Non-Photochemical Quenching in Chloroplasts

Plants convert solar energy into chemical energy through photosynthesis, which supports almost all life activities on earth. Because the intensity and quality of sunlight can change dramatically throughout the day, various regulatory mechanisms help plants adjust their photosynthetic output accordingly, including the regulation of light energy accumulation to prevent the generation of damaging reactive oxygen species. Non-photochemical quenching (NPQ) is a regulatory mechanism that dissipates excess light energy, but how it is regulated is not fully elucidated. Herein, we report a new NPQ-regulatory protein named Day-Length-dependent Delayed-Greening1 (DLDG1). The Arabidopsis DLDG1 associates with the chloroplast envelope membrane, and the dldg1 mutant had a large NPQ value compared with wild type. The mutant also had a pale-green phenotype in developing leaves but only under continuous light; this phenotype was not observed when dldg1 was cultured in the dark for [≥]8 h per day. DLDG1 is a homolog of the plasma-membrane-localizing cyanobacterial proton-extrusion-protein A that is required for light-induced H+ extrusion, and also shows similarity in its amino-acid sequence to that of Ycf10 encoded in the plastid genome. Arabidopsis DLDG1 enhances the growth-retardation phenotype of the Escherichia coli K+/H+ antiporter mutant, and the everted membrane vesicles of the E. coli expressing DLDG1 show the K+/H+ antiport activity. Our findings suggest that DLDG1 functionally interacts with Ycf10 to control H+ homeostasis in chloroplasts, which is important for the light-acclimation response, by optimizing the extent of NPQ.

plant biology↗

bioRxiv2018

Heterotypic inter-GPCR β-arrestin coupling regulates lymphatic endothelial junctional architecture in murine lymph nodes

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) activate G protein-coupled receptors (GPCRs) to regulate key pathobiological processes. Here we report a novel lipid mediator GPCR cross-talk mechanism that modulates lymphatic endothelial junctional architecture in lymph nodes. LPAR1 was identified as an inducer of S1PR1/ {beta}-arrestin coupling from a genome-wide CRISPR/ Cas9 transcriptional activation screen. LPAR1 activation induced S1PR1 {beta}-arrestin recruitment while suppressing Gi protein signaling. Lymphatic endothelial cells from cortical and medullary sinuses of lymph nodes which express LPAR1 and S1PR1, exhibit porous junctional architecture and constitutive S1PR1 coupling to {beta}-arrestin which was suppressed by the LPAR1 antagonist AM095. In endothelial cells, LPAR1-activation increased trans-endothelial permeability and junctional remodeling from zipper-like structures to puncta of adhesion plaques that terminate at actin-rich stress fibers with abundant intercellular gaps. Cross-talk between LPA and S1P receptors regulates complex junctional architecture of lymphatic sinus endothelial cells, a site of high lymphocyte traffic and lymph flow.

cell biology↗