Biology subjects

Seo, M.

Publications and source records attributed to Seo, M..

17 recordsLinked to original sources

bioRxiv2026

Root-to-shoot ABA transport by NPF2.4 and NPF2.5 links stomatal regulation to photosynthetic performance

Fluctuating light strongly limits photosynthetic efficiency in plants, yet the mechanisms coordinating stomatal dynamics with rapid photosynthetic induction remain incompletely understood. Here, through a forward physiological screen in Arabidopsis, we identify the abscisic acid (ABA) transporters NPF2.4 and NPF2.5 as regulators of photosynthetic responses to fluctuating light. Loss-of-function npf2.4 and npf2.5 mutants exhibited accelerated stomatal opening and photosynthetic induction during light transitions, resulting in enhanced biomass accumulation and seed yield without compromising long-term drought tolerance. NPF2.4 and NPF2.5 mediated ABA uptake in yeast and were predominantly expressed in the root pericycle and cortex/epidermal tissues, respectively. Reciprocal grafting, xylem sap ABA measurements, and ABA treatment to the roots demonstrated that both transporters regulate root-to-shoot ABA transport. Our findings reveal that root-derived ABA modulates stomatal dynamics and photosynthetic efficiency under fluctuating light, establishing long-distance hormone transport as a key regulator of plant carbon gain in dynamic environments.

plant biology↗

bioRxiv2026

Cascaded Nano-ring Dialyzer for Continuous Regenerative Peritoneal Dialysis

End-stage kidney disease (ESKD) requires lifelong kidney replacement therapy, yet conventional hemodialysis and peritoneal dialysis remain limited by intermittent treatment, restricted mobility, and repeated dialysate exchange. Here, we developed a continuous regenerative peritoneal dialysis platform based on a nano-ring-assisted nanoelectrokinetic dialyzer for portable artificial kidney applications. We first identified key geometric and electrokinetic parameters governing the removal performance of nano-ring meshes, including mesh dimension, nano-ring coating thickness, the number of cascaded nano-rings, and the relative orientation between fluid flow and the applied electric field. We then developed a single nano-ring dialyzer operating at 1.33 mL/min and scaled the treatment capacity to approximately 10 mL min/min through parallel integration of multiple modules. In a canine model, the closed-loop system achieved approximately 10 % reduction in circulating uremic toxin levels during continuous treatment. We further improved the biocompatibility of the regenerated dialysate by integrating plate-type electrodes, activated carbon, bicarbonate buffering, and UV-C treatment. In an unanesthetized canine model, the improved system sustained continuous toxin removal for 4 h while major hepatic and inflammatory markers remained within recoverable ranges. These results demonstrate that cascaded nano-ring enables continuous dialysate regeneration with scalable throughput, reduced dependence on fresh dialysate, and in vivo control of uremic toxins, providing a technological foundation for portable or wearable regenerative peritoneal dialysis systems.

bioengineering↗

bioRxiv2026

Water stress adaptive responses in plants require movement of ABA and AB-aldehyde from vascular to target tissues

Vascular plants rapidly coordinate root and shoot responses to water stress. Abscisic acid (ABA) mediates these adaptations; however, it remains unclear which cells produce ABA, whether ABA synthesis shifts during stress, and whether ABA movement is required for its adaptive functions. Here, we map ABA biosynthesis at cellular resolution in Arabidopsis and report that water-stress adaptive responses in roots and shoots require movement of ABA and its precursor AB-aldehyde from vascular tissues to target cells. We suggest that ABA accumulation arises from two parallel routes: (i) ABA synthesized in the vasculature via ABA2 and AAO3, then moving to guard cells, and (ii) phloem-derived AB-aldehyde being converted to ABA in the epidermis or bundle sheath by AAO1 and AAO2. Finally, we predict that tightly packed cells beneath leaf veins facilitate efficient ABA delivery to guard cells, an anatomical arrangement that has enabled angiosperms to evolve the use of ABA to rapidly close stomata.

plant biology↗

bioRxiv2026

Lyophilization Maintains the Storage Stability and Bioactivity of Mesenchymal Stem Cell–Derived Extracellular Vesicles

BackgroundExtracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are emerging therapeutic candidates for bone regeneration, but their long-term stability remains a barrier to clinical translation. This study evaluated whether lyophilization supports the stable storage of extracellular vesicles derived from human epidural fat MSCs (hEF-MSCs) cell line. Research Design and MethodsEVs were isolated, lyophilized with 8.5 % sucrose and HEPES(4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, N-(2-Hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid)), and stored for 3 months at -80, -20, 4, and room temperature (20). After reconstitution in phosphate-buffered saline (PBS), structural characteristics were assessed using transmission electron microscopy, nanoparticle tracking analysis, and flow cytometry. Functional activity was evaluated using MC3T3-E1 osteogenic differentiation assays. The main outcome measures included morphology, particle counts, marker expression, cytotoxicity, and sequencing profiles. ResultsLyophilization maintained EV morphology, structural integrity, and particle distribution across all storage temperatures. Marker expression remained comparable among the conditions. Reconstituted EVs promoted osteogenic differentiation of MC3T3-E1 cells without evidence of cytotoxicity. Sequencing profiles revealed no significant differences among storage conditions. ConclusionsLyophilized EVs from hEF-MSCs cell lines exhibited stable structural and functional properties across a range of storage temperatures, supporting their suitability for further development in bone regeneration applications.

Molecular Biology↗

bioRxiv2026

Lyophilized Extracellular Vesicles Retain Regenerative Activity and Accelerate Wound Healing

Extracellular vesicles (EVs) are promising therapeutic agents for tissue regeneration because they regulate intercellular communication and modulate inflammatory responses. However, preserving EV bioactivity during long-term storage remains a major barrier to clinical application. We examined whether lyophilized EVs stored at -80 {degrees}C maintain their structural integrity and therapeutic efficacy in an in vivo wound-healing model. Mesenchymal stem cell-derived EVs were isolated and freeze-dried before storage at -80 {degrees}C. We evaluated EV physicochemical characteristics before and after lyophilization using nanoparticle tracking analysis, transmission electron microscopy, and EV marker-expression analysis. To assess regenerative efficacy, lyophilized EVs were applied topically to full-thickness ear wounds in CCR2-GFP mice. Wound-healing progression and CCR2-positive cell infiltration were monitored during tissue recovery using intravital microscopy. Lyophilized EVs preserved their characteristic morphology, particle-size distribution, and EV surface marker expression after storage. In vivo analysis showed that EV-treated wounds closed significantly faster than phosphate-buffered saline-treated controls. Additionally, lyophilized EV treatment reduced CCR2-positive inflammatory cell recruitment during healing, suggesting an immunomodulatory role in tissue regeneration. These findings show that EVs lyophilized and stored at -80 {degrees}C retain biological function and therapeutic potential in vivo. Lyophilized EVs may, therefore, provide a practical strategy for long-term storage and delivery of EV-based regenerative therapeutics.

Cell Biology↗

bioRxiv2025

NPF4.6-mediated ABA transport modulates stomatal responses to fluctuating light

Stomatal responses to fluctuating light (FL) strongly influence photosynthetic efficiency and biomass accumulation in seed plants. The abscisic acid (ABA) transporter NPF4.6 (also known as NRT1.2 or AIT1) mediates hormone import into guard cells, but its physiological roles in leaves remain unclear. Here, we examined the functions of NPF4.6 in Arabidopsis thaliana by characterizing two independent loss-of-function mutants (npf4.6) under both steady and FL conditions. Compared with wild type, npf4.6 showed a 21-43% reduction in the half-time of stomatal opening and a 26-32% increase in the mean net CO2 assimilation rate under simulated field light conditions, resulting in a 41-48% increase in shoot biomass. In contrast, no marked differences in photosynthetic efficiency were observed between the wild type and npf4.6 under drought stress, suggesting that the role of NPF4.6 is more pronounced under well-watered, dynamic-light conditions. Overall, these findings demonstrate that NPF4.6 contributes to the fine-tuning of stomatal kinetics under variable light environments, and highlight hormone transport as a promising target for improving photosynthesis and growth in the field.

plant biology↗

bioRxiv2025

Thiamine transporter 2 and Janus kinase 2 inhibitor, fedratinib suppresses thermogenic activation of human neck area-derived adipocytes

IntroductionBrown adipocytes consume higher amounts of metabolic substrates and regulators including thiamine during adrenergic stimulation supporting heat generation. Our previous findings showed that fedratinib, a potent inhibitor of thiamine transporter (ThTr) 2 and Janus kinase 2 (JAK2), reduced thermogenic activity; however, the underlying molecular mechanisms remain elusive. MethodsPrimary human subcutaneous (SC) and deep neck (DN)-derived adipocytes were treated with dibutyryl (db)-cAMP, fedratinib, or the combination of the two compounds after differentiation. Global transcriptomic analysis was performed by bulk RNA-sequencing. Differentially expressed genes were subjected to pathway enrichment analysis. We also utilized publicly available single-cell RNA-sequencing datasets and adiposetissue.org to correlate ThTr2 expression in adipose tissue to clinical parameters of patient cohorts. Amino acid flux was measured by metabolomics. Results and discussionThTr2 expression was observed exclusively enriched in the adipocytes cluster within human brown and white adipose tissue. In response to ThTr2 inhibition, the db-cAMP-stimulated upregulation of the canonical thermogenic markers and proton leak respiration, which associates with UCP1-dependent heat generation, was prevented in both adipocyte types. RNA-sequencing found 40 and 41 downregulated genes potentially underlying the metabolic changes in SC and DN-derived adipocytes, respectively, which were involved in various biological pathways, including transcriptional regulation of brown and beige adipocytes differentiation, signaling by interleukins, nicotinamide salvaging, and gene and protein expression by JAK/STAT signaling after interleukin-12 stimulation. The expression of recently identified thermogenesis regulators, such as transglutaminase (TGM) 2 and inhibitor of DNA binding (ID) 1, was also abrogated by ThTr2 inhibition during adrenergic stimulation. Intriguingly, glutamate transporter (GLT) 1 and L-amino acid transporter (LAT) 2 expression was also attenuated by fedratinib, restricting amino acid consumption. Finally, we found that the expression of ThTr2 in human white adipose tissue was inversely correlated with body mass index, waist-hip ratio, leptin secretion, and plasma insulin, glucose, cholesterol and triacylglycerol levels, supporting the importance of thiamine metabolism in adipocyte and metabolic health. O_LIFedratinib prevented adrenergic-stimulated upregulation of thermogenic genes. C_LIO_LIThe consumption of amino acids and the expression of their transporters decreased by fedratinib during adrenergic stimulation. C_LIO_LIOxygen consumption and proton leak respiration reflecting heat generation were abrogated by fedratinib. C_LI

cell biology↗

bioRxiv2025

Iron uptake mediated by TFRC and secretion of transferrin types stimulate thermogenic activation in human adipocytes

Adrenergic-driven thermogenic activation of brown adipose tissue requires high amounts of nutrients including iron supporting mitochondrial biogenesis. This was governed by rapid gene expression changes in human cervical-derived brown adipocytes. Transferrin receptor 1 (TFRC) was strongly upregulated in response to dibutyryl-cAMP. Pharmacological inhibition and siRNA-mediated knockdown of TFRC during adrenergic stimulation decreased intracellular iron content and prevented elevation of oxygen consumption and induction of thermogenic markers. Deferoxamine-mediated iron chelation also showed comparable effects. Contrarily, the expression of ferroportin iron exporter was suppressed during activation, however, its pharmacological inhibition did not further increase thermogenesis. Brown adipocytes constitutively expressed and secreted high amounts of transferrin while the released melanotransferrin at activated condition was predicted to further augment iron influx stimulating heat production.

cell biology↗

bioRxiv2025

Sensitizing tumor response to topoisomerase I antibody drug conjugate by selective CDK7 inhibition

This study investigates the transcriptional impact of Q901, a highly selective CDK7 inhibitor in clinical development. Q901 primarily disrupted MYC and E2F-dependent transcription program, downregulating cell cycle control and DNA damage repair pathways. CDK7 binding at the promoter-proximal regions was dramatically stabilized by Q901, leading to reduced occupancy of MYC, E2F, and RNA Polymerase II (RNAPII). These findings offered a novel therapeutic strategy to enhance cancer susceptibility to TOP1-DNA protein crosslinks (TOP1-DPCs) induced by TOP1 inhibitors. Resistance to TOP1 inhibitors arises through activation of DNA repair pathway when elongating RNAPII encounters TOP1-DPCs. By suppressing RNAPII transition from initiation to elongation and DNA repair pathways, Q901 stabilizes TOP1-DPCs and sensitizes tumor to TOP1 inhibitors. Preclinical studies demonstrated enhanced tumor suppression when combining Q901 with TOP1 inhibitor-based antibody-drug conjugates (TOP1i-ADCs), highlighting its potential as a therapeutic option for cancers resistant to TOP1i-ADC therapy. TeaserOvercoming ADC cross-resistance through combination approach.

cancer biology↗

bioRxiv2024

Anatomical Region-Specific Transcriptomic Signatures and the Role of Epithelial Cells in Pterygium Inflammation: A Multi-Omics Analysis

BackgroundThe anatomy of pterygium consists of the head, neck, and body. Prior studies have examined the three parts collectively, yet the treatment methods and their success rates differ based on the anatomical characteristics. In this study, we divide the pterygium tissue into Main (head and neck) and Acc (body) to investigate its pathogenesis across regions. PurposesThis study aims to understand the pathogenesis and identify potential therapeutic targets of pterygium. Through a robust multi-omics analysis of bulk and single-cell RNA sequencing (RNA-seq) data from pterygium patients, we focus on the expression of inflammatory and mitochondrial energy pathways and identify potential genes responsible for the upregulated pathways in pterygium. MethodsWe collected bulk RNA-seq data from six pterygium patients and single-cell RNA-seq data from two pterygium patients. We then investigated the pathway enrichment, pathway correlation, differential gene expressions, protein-protein interactions, and cell-cell communications of pterygium. ResultsFrom the analysis of bulk RNA-seq data, the distribution of sample points from the principal component analysis plot and the pathways enriched from the Gene Ontology analysis showed distinct expression patterns in the Acc group compared to the Main and control groups. This suggested the need to separate the Main and Acc regions within pterygium samples and utilize single-cell RNA-seq data to understand the differences between the Main and control groups that the bulk data could not capture. The annotation of integrated single-cell data revealed a cluster of epithelial cells containing only pterygium samples. Cells from this cluster exhibited significant contributions to the ANGPTL, IL1, and KLK signaling networks in the cell-cell communication analysis. We also observed significant upregulation of the cells in the inflammatory pathways related to integrated stress response and the renin-angiotensin-aldosterone system, both of which showed high correlations with energy metabolism pathways. Significant changes in the expression of multiple pro-inflammatory, antioxidant, and immune-related genes were also identified. ConclusionThe different expression patterns between the Main and Acc groups suggest the need to consider different anatomical regions separately in future studies of pterygium. Additionally, the significant role epithelial cells from the Main group play in the inflammation of pterygium presents a potential clinical approach to the disease.

bioinformatics↗

bioRxiv2023

Orchid seed germination through auto-activation of mycorrhizal symbiosis signaling regulated by gibberellin

Orchids parasitically depend on external nutrients from mycorrhizal fungi for seed germination. Previous findings suggest that orchids utilize a genetic system of mutualistic arbuscular mycorrhizal (AM) symbiosis to establish parasitic symbiosis. In AM symbiosis, recent studies have revealed that the plant hormone gibberellin (GA) negatively affects fungal colonization and development. Although previous studies imply that GA is important for orchid mycorrhizal symbiosis, the molecular mechanism of seed germination in which mycorrhizal symbiosis co-occurs remains unclear because, in AM plants, GA regulates seed germination and symbiosis positively and negatively, respectively. To elucidate this conflict, we investigated the effect of GA on Bletilla striata seed germination and mycorrhizal symbiosis using asymbiotic and symbiotic germination methods. Additionally, we compared the transcriptome profiles between asymbiotically and symbiotically germinated seeds. Exogenous GA negatively affected seed germination and fungal colonization, and endogenous bioactive GA was actively converted to the inactive form during seed germination. Transcriptome analysis showed that B. striata shared many of the induced genes between asymbiotically and symbiotically germinated seeds, including GA metabolism- and signaling-related genes and AM-specific marker homologs. Our study suggests that orchids have evolved in a manner that they do not use bioactive GA as a positive regulator of seed germination and instead, auto-activate the mycorrhizal symbiosis pathway through GA inactivation to accept the fungal partner immediately during seed germination.

plant biology↗

bioRxiv2022

Complete loss of RelA and SpoT homologs in Arabidopsis reveals the importance of the plastidial stringent response in the interplay between chloroplast metabolism and plant defense response

The highly phosphorylated nucleotide, guanosine tetraphosphate (ppGpp), functions as a secondary messenger in bacteria and chloroplasts. The accumulation of ppGpp alters plastidial gene expression and metabolism, which are required for proper photosynthetic regulation and robust plant growth. However, because four plastid-localized ppGpp synthases/hydrolases function redundantly, the impact of the loss of ppGpp-dependent stringent response on plant physiology remains unclear. We used the CRISPR/Cas9 technology to generate an Arabidopsis thaliana mutant lacking all four ppGpp synthases/hydrolases, and characterized its phenotype. The mutant showed 20-fold less ppGpp levels than the wild type (WT) under normal growth conditions, and exhibited leaf chlorosis and increased expression of defense-related genes as well as salicylic acid and jasmonate levels upon transition to nitrogen-starvation conditions. These results demonstrate that proper levels of ppGpp in plastids are required for controlling not only plastid metabolism but also phytohormone signaling, which is essential for plant defense.

plant biology↗

bioRxiv2021

Chitin-induced systemic disease resistance in rice requires both OsCERK1 and OsCEBiP and is mediated via perturbation of cell-wall biogenesis in leaves

O_LIChitin is a well-known elicitor of disease resistance whose recognition by plants is crucial to perceive fungal infections. Chitin can induce both a local immune response and a systemic disease resistance when provided as a supplement in soils. Unlike local immune responses, how chitin-induced systemic disease resistance is deployed has not been studied in detail. C_LIO_LIIn this study, we evaluated systemic disease resistance against the fungal pathogen Bipolaris oryzae by performing a transcriptome analysis and monitoring cell-wall composition in rice plants grown in chitin-supplemented soils. We also examined the local immune response to chitin by measuring the production of reactive oxygen species in leaves. C_LIO_LIChitins induced both local immune response and systemic disease resistance with differing requirements for the receptors OsCERK1 and OsCEBiP. Transcriptome analysis suggested that a perturbation in cell-wall biogenesis is involved in the induction of systemic disease resistance, an idea which was supported by the induction of disease resistance by treatment with a cellulose biosynthesis inhibitor and alterations of cell-wall composition. C_LIO_LIThese findings suggest that chitin-induced systemic disease resistance in rice is caused by a perturbation of cell-wall biogenesis in leaves through long-distance signalling after recognition of chitins by OsCERK1 and OsCEBiP. C_LI

plant biology↗

bioRxiv2021

Guanosine-specific single-stranded ribonuclease effectors of a phytopathogenic fungus potentiate host immune responses

Plants activate immunity upon recognition of pathogen-associated molecular patterns. Although phytopathogens have evolved a set of effector proteins to counteract plant immunity, some effectors are perceived by hosts and induce immune responses. Here, we show that two secreted ribonuclease effectors, SRN1 and SRN2, encoded in a phytopathogenic fungus, Colletotrichum orbiculare, induce cell death in a signal peptide- and catalytic residue-dependent manner, when transiently expressed in Nicotiana benthamiana. The pervasive presence of SRN genes across Colletotrichum species suggested the conserved roles. Using a transient gene expression system in cucumber (Cucumis sativus), an original host of C. orbiculare, we show that SRN1 and SRN2 potentiate host pattern-triggered immunity. Consistent with this, C. orbiculare SRN1 and SRN2 deletion mutants exhibited increased virulence on the host. In vitro analysis revealed that SRN1 specifically cleaves single-stranded RNAs at guanosine, leaving a 3'-end phosphate. This activity has not been reported in plants. Importantly, the potentiation of C. sativus responses by SRN1 and SRN2 depends on the signal peptide and ribonuclease catalytic residues, suggesting that secreted SRNs cleave RNAs in apoplast and are detected by the host. We propose that the pathogen-derived apoplastic guanosine-specific single-stranded endoribonucleases lead to immunity potentiation in plants.

microbiology↗

bioRxiv2020

The Arabidopsis NRT1/PTR FAMILY Protein NPF7.3/NRT1.5 is an Indole-3-butyric Acid Transporter Involved in Root Gravitropism

Active membrane transport of plant hormones and their related compounds is an essential process that determines the distribution of the compounds within plant tissues and, hence, regulates various physiological events. Here, we report that the Arabidopsis NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY 7.3 (NPF7.3) protein functions as a transporter of indole-3-butyric acid (IBA), a precursor of the major endogenous auxin indole-3-acetic acid (IAA). When expressed in yeast, NPF7.3 mediated cellular IBA uptake. Loss-of-function npf7.3 mutants showed defective root gravitropism with reduced IBA levels and auxin responses. Nevertheless, the phenotype was restored by exogenous application of IAA but not by IBA treatment. NPF7.3 was expressed in pericycle cells and the root tip region including root cap cells of primary roots where the IBA-to-IAA conversion occurs. Our findings indicate that NPF7.3-mediated IBA uptake into specific cells is required for the generation of appropriate auxin gradients within root tissues.

plant biology↗

bioRxiv2020

The tomato DELLA protein PROCERA promotes ABA responses in guard cells by upregulating ABA transporter

Plants reduce transpiration to avoid drought stress by stomatal closure. While abscisic acid (ABA) has a central role in the regulation of stomatal closure under water-deficit conditions, we demonstrated in tomato that the gibberellin (GA) response inhibitor, the DELLA protein PROCERA (PRO), promotes ABA-induced stomatal closure and gene transcription in guard cells. To study how PRO affects stomatal closure, we performed RNAseq analysis of isolated guard cells and identified the ABA transporters ABA-IMPORTING TRANSPORTER1.1 (AIT1.1) and AIT1.2, also called in Arabidopsis NPF4.6, as upregulated by PRO. Tomato has four AIT1 genes, but only AIT1.1 and AIT1.2 were upregulated by PRO, and only AIT1.1 exhibited high expression in guard cells. Functional analysis of AIT1.1 in yeast confirmed its activity as an ABA transporter, possibly importer. CRISPR-Cas9-defrived ait1.1 mutant exhibited increased transpiration, larger stomatal aperture and reduced response to ABA. Moreover, ait1.1 suppressed the promoting effects of PRO on ABA-induced stomatal closure and gene expression in guard cells. The negative interaction between GA and ABA has been studied for many years in numerous plant species. These studies suggest that the crosstalk is mediated by changes in hormone biosynthesis and signaling. Our results suggest that it is also mediated by changes in hormone transport. One-sentence SummaryThe tomato DELLA protein PROCERA promoted abscisic acid-induced stomatal closure and gene expression by upregulating the expression of the ABA transporter ABA-IMPORTING TRANSPORTER 1 in guard cells.

plant biology↗

bioRxiv2018

Novel Data Transformations for RNA-seq Data Analysis

We propose eight data transformations for RNA-seq data analysis aiming to make the transformed sample mean to be representative of the distribution center since it is not always possible to transform count data to satisfy the normality assumption. Simulation studies showed that limma based on transformed data by using the rv transformation (denoted as limma+rv) performed best compared with limma based on transformed data by using other transformation methods in term of high accuracy and low FNR, while keeping FDR at the nominal level. For large sample size, limma based on transformed data by using the 8 proposed transformation methods had similar performance to limma based on transformed data by using existing transformation methods for equal library size scenarios. Otherwise, limma based on transformed data by using the rv, lv, rv2, or lv2 transformation, or by using the existing voom transformation performed better than limma based on data from other transformation methods. Real data analysis results showed that limma+ l2 performed best, while limma+ rv also had good performance.

bioinformatics↗