Biology subjects

Kim, S.-C.

Publications and source records attributed to Kim, S.-C..

10 recordsLinked to original sources

bioRxiv2026

Secreted phospholipase A2α generates a pathogen-derived lysophospholipid to signal local immunity

In plants, effector-triggered immunity (ETI) is initiated when NLR receptors recognize pathogen effectors, yet the molecular signals linking this recognition to downstream defense activation remain poorly defined, in contrast to the well-characterized immunogenic signals of pattern-triggered immunity. Here, we show that a lysophospholipid is a previously unidentified ETI-mediating immune signal generated through host enzymatic conversion of pathogen membrane lipids. Upon recognition of avirulent Pseudomonas syringae, secretory phospholipase A2 (PLA2) is rapidly induced and secreted into the apoplast, where it hydrolyzes bacterial phosphatidylethanolamine to produce lysophosphatidylethanolamines (LPEs), predominantly LPE18:1. Genetic ablation of PLA2 compromises local immunity, hypersensitive response confinement, and defense gene activation, all of which are largely rescued by exogenous LPE18:1. Mechanistically, LPE18:1 promotes ICS1-dependent salicylic acid biosynthesis and NPR1-mediated transcriptional reprogramming. Together, these findings support pathogen-derived LPE18:1 as a newly identified lipid-based immune signal that links NLR activation to spatially confined defense responses. The evolutionary conservation of secretory PLA2 enzymes and lysophospholipid signaling from plants to mammals suggests that host-directed enzymatic remodeling of pathogen membranes into immune-activating lipid signals may constitute a conserved strategy of innate immunity.

plant biology↗

bioRxiv2025

New insights into the role of oxytocin signaling in preeclampsia

BackgroundOxytocin signaling may play an important role in the human placenta during pregnancy, where abnormal function can cause pregnancy complications such as preeclampsia, a hypertension syndrome with elusive etiology, treatment, and diagnosis. As pregnancy progresses, the clinical effects of high blood pressure tend to worsen. Therefore, an early diagnosis of preeclampsia is necessary for a successful pregnancy. MethodThis study examined placenta and plasma samples from normal and preeclamptic pregnancies, approved by the Institutional Review Board. qRT-PCR, western blot, ELISA, gelatin zymography, and ChIP were performed on placental tissues. JEG-3 cells and HUVECs were cultured under normoxia or hypoxia with oxytocin or atosiban. siRNA/miRNA transfections and RUPP rat models assessed oxytocins effects. Data were analyzed using ANOVA and Duncans test (P [≤] 0.05) in SPSS. ResultHere, we assessed the effects of oxytocin signaling on key placental functions and its correlation with preeclampsia, revealing a significant association with placental dysfunction. Our findings revealed that oxytocin increased trophoblast invasion via ERK1/2- and JNK/AP-1-dependent pathways. Notably, oxytocin signaling was inhibited by hsa-miR-193b-5p and hypoxia. Administering atosiban to pregnant rats hindered placental invasion activity, mirroring symptoms of preeclampsia, and disrupted placental development. Finally, we examined oxytocin signaling in patients with preeclampsia by analyzing oxytocin levels in the first trimester. Oxytocin levels were higher in those who later developed preeclampsia than normal pregnant women. ConclusionThese results indicate that changes in oxytocin signaling are related with preeclampsia throughout pregnancy, emphasizing its potential as a novel early diagnostic biomarker.

pathology↗

bioRxiv2024

Genomic insights into the evolution and adaptation of the memorial roses (Rosa lucieae; Rosaceae) in saline environments

Rosa lucieae (syn. Rosa wichurana or R. wichuraiana; Rosaceae) is one of the major wild progenitors of modern rose cultivars. In breeding roses, R. lucieae has contributed not only to white blooms and shiny leaves, but most of all, to succeed in various harsh conditions and high resistance to diseases and pests. The wild R. lucieae inhabits littoral sand banks or rocks, where drought stress and high salinity inhibit plant growth. In this study, we assembled the chromosome-level genome sequence of a wild accession of R. lucieae and identified potential genes that may responsible for the evolution of salt tolerance. Within the 544.7 Mb-long genome of R. lucieae, recent duplications and divergence of the genes responsible to stress tolerance were identified, including stress response, signaling, homeostasis, and detoxification. Additionally, the gene family evolution analyses elucidated rapid evolution of stress tolerant functions in R. lucieae. The first high-quality genome assembly of wild R. lucieae contributes significantly to our understanding of the genomic evolution and adaptive mechanism of R. lucieae, which promises the enhancement of our efforts in rose breeding programs.

plant biology↗

bioRxiv2024

Identification of Arabidopsis phospholipase Ds involved in circadian clock alterations using CRISPR/Cas9-based multiplex editing

Reciprocal regulation between the circadian clock and lipid metabolism is emerging, but its mechanisms remain elusive. We reported that a lipid metabolite phosphatidic acid (PA) bound to the core clock transcription factors LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and chemical suppression of phospholipase D (PLD)-catalyzed PA formation perturbed the clock in Arabidopsis. Here, we identified, among 12 members, specific PLDs critical to regulating clock function. We approached this using a multiplex CRISPR/Cas9 system to generate a library of plants bearing randomly mutated PLDs, then screening the mutants for altered rhythmic expression of CCA1. All PLDs, except for {beta}2, were effectively edited, and the mutations were heritable. Screening of T2 plants identified some with an altered rhythm of CCA1 expression, and this trait was observed in many of their progenies. Genotyping revealed that at least two of six PLDs (1, 3,{gamma} 1,{delta} ,{varepsilon} and{zeta} 2) were mutated in the clock-altered plants. Those plants also had reduced levels of PA molecular species that bound LHY and CCA1. This study identifies combinations of two or more PLDs and changes in particular phospholipid species involved in clock outputs and also suggests a functional redundancy of the six PLDs for regulating the plant circadian clock. One sentence summaryThis study identifies combinations of two or more phospholipase Ds involved in altering clock outputs and the specific phosphatidic acid species impacting the clock rhythms.

plant biology↗

bioRxiv2023

Pan-cancer analysis reveals multifaceted roles of retrotransposon-fusion RNAs

Transposon-derived transcripts are abundant in RNA sequences, yet their landscape and function, especially for fusion transcripts derived from unannotated or somatically acquired transposons, remains underexplored. Here, we developed a new bioinformatic tool to detect transposon-fusion transcripts in RNA-sequencing data and performed a pan-cancer analysis of 10,257 cancer samples across 34 cancer types as well as 3,088 normal tissue samples. We identified 52,277 cancer-specific fusions with [~]30 events per cancer and hotspot loci within transposons vulnerable to fusion formation. Exonization of intronic transposons was the most prevalent genic fusions, while somatic L1 insertions constituted a small fraction of cancer-specific fusions. Source L1s and HERVs, but not Alus showed decreased DNA methylation in cancer upon fusion formation. Overall cancer-specific L1 fusions were enriched in tumor suppressors while Alu fusions were enriched in oncogenes, including recurrent Alu fusions in EZH2 predictive of patient survival. We also demonstrated that transposon-derived peptides triggered CD8+ T-cell activation to the extent comparable to EBV viruses. Our findings reveal distinct epigenetic and tumorigenic mechanisms underlying transposon fusions across different families and highlight transposons as novel therapeutic targets and the source of potent neoantigens.

cancer biology↗

bioRxiv2022

Circadian clock factors regulate seed oil accumulation by promoting fatty acid synthesis in Arabidopsis

The circadian clock regulates temporal metabolic activities, enabling organisms to adapt to cyclic environmental changes, but how it affects lipid metabolism in plants is poorly understood. Our previous finding showed that the central clock transcription factors LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) increased seed oil contents in Arabidopsis. Here we investigated the molecular and metabolic mechanism underlying the LHY and CCA1 regulated oil accumulation. Triacylglycerol (TAG) accumulation in Arabidopsis developing seeds was increased in LHY-overexpressing (LHY-OE) and decreased in lhycca1 plants compared to wild-type (WT). Metabolic tracking of lipids in developing seeds indicated that fatty acids (FAs) of major lipid precursors for TAG production increased more rapidly in LHY-OE and slowly in lhycca1 than in WT, suggesting that LHY enhanced FA synthesis. Transcript analysis revealed that the expression of genes involved in FA synthesis, including the one encoding {beta}-ketoacyl-ACP synthase III (KASIII), was oppositely changed in developing seeds of LHY/CCA1-OEs and those of lhycca1. Chromatin immunoprecipitation, electrophoretic mobility shift, and transactivation assays indicated that LHY directly bound and activated the promoter of KASIII. Furthermore, phosphatidic acid, a metabolic precursor to TAG, inhibited LHY binding to KASIII promoter elements. Our data reveal a new regulatory mechanism by the core clock regulators for storage lipid production during plant seed development.

biochemistry↗

bioRxiv2022

Lipid-mediated nuclear moonlighting of cytosolic glyceraldehyde-3-phosphate dehydrogenase in plant heat response

Cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC) is a glycolytic enzyme, but it undergoes stress-induced nuclear translocation for moonlighting and regulating gene expression. To elucidate how the cytosolic enzyme moves into the nuclei under stress, we show that the plasma membrane-associated phospholipase D{delta}(PLD{delta}) and its product phosphatidic acid (PA) promote heat-induced nuclear translocation of GAPC. The GAPC nuclear accumulation and Arabidopsis seedling tolerance to heat stress were reduced in pld{delta}, which was restored by genetic complementation with intact PLD{delta}, but not with catalytically inactive enzyme. GAPC overexpression enhanced the seedling thermotolerance and the expression of heat-inducible genes, but this was not observed when GAPC was overexpressed in the pld{delta} background. The GAPC nuclear accumulation and seedling thermotolerance were also decreased by application with a vesicle trafficking inhibitor brefeldin A (BFA) or zinc that inhibited the PA-GAPC interaction. Heat stress elevated PA levels in nuclei from wild-type, but not from pld{delta} and BFA-treated plants. Lipid labeling and fluorescence resonance energy transfer analyses demonstrated heat-induced nuclear co-localization of PA and GAPC, which was impaired by BFA or zinc treatment. Taken together, our data suggest that PLD{delta}-produced PA mediates nuclear translocation of GAPC via lipid-protein interaction and vesicle trafficking for plants to cope with heat. One sentence summaryThe lipid mediator phosphatidic acid produced by a plasma membrane-associated phospholipase D mediates the nuclear moonlighting of cytosolic glyceraldehyde-3-phosphate dehydrogenase under heat.

plant biology↗

bioRxiv2021

Therapeutic base and prime editing of COL7A1 mutations in recessive dystrophic epidermolysis bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by loss-of-function mutations in the COL7A1 gene, which encodes type VII collagen (C7), a protein that functions in skin adherence. From 36 Korean RDEB patients, we identified a total of 69 pathogenic mutations (40 variants without recurrence), including point mutations (72.5%) and insertion/deletion mutations (27.5%). We used base and prime editing to correct mutations in fibroblasts from two patients (Pat1, who carried a c.3631C>T mutation in one allele, and Pat2, who carried a c.2005C>T mutation in one allele). We applied adenine base editors (ABEs) to correct the pathogenic mutation or to bypass a premature stop codon in Pat1-derived primary fibroblasts. To expand the targeting scope, we also utilized prime editors (PEs) to correct the mutations in Pat1- and Pat2-derived fibroblasts. Ultimately, we found that both ABE- and PE-mediated correction of COL7A1 mutations restored full-length C7 expression, reversed the impaired adhesion and proliferation exhibited by the patient-derived fibroblasts, and, following transfer of edited patient-derived fibroblasts into the skin of immunodeficient mice, led to C7 deposition within the dermal-epidermal junction. These results suggest that base and prime editing could be feasible strategies for ex vivo gene editing to treat RDEB.

bioengineering↗

bioRxiv2021

Correlated Drug Action as a Baseline Additivity Model for Combination Cancer Therapy in Patient Cohorts and Cell Cultures

Identifying and characterizing the effect of combination therapies is of paramount importance in various diseases, including cancer. Various competing null models have been proposed to serve as baselines against which to compare the effect of drug combinations. In this work, we introduce Correlated Drug Action (CDA), a baseline model for the study of drug combinations in both cell cultures and in patient populations. CDA assumes that the efficacy of pairs of drugs to be used in a combination may be correlated, that is, if the efficacy of a drug in a given patient or cell is high (low), then the efficacy of the other drug may also be high (low) in the same patient or cell. Our model can be used in the temporal domain (temporal CDA or tCDA) to explain survival curves in patient populations, and in the dose domain (dose CDA or dCDA), to explain dose-response curves in cell cultures. At the level of clinical trials, we demonstrate tCDAs utility in identifying possibly synergistic combinations and cases where the combination can be explained in terms of the monotherapies. At the level of cells in culture, dCDA generalizes null models such as Bliss independence, the Highest Single Agent model, the dose equivalence principle, and is consistent with what should be expected in sham combinations. We demonstrate the applicability of dCDA in assessing combinations in experimental MCF7 cell-line data by introducing a new metric, the Excess over CDA (EOCDA).

bioinformatics↗

bioRxiv2021

JAG1 intracellular domain acts as a transcriptional cofactor that forms an oncogenic transcriptional complex with DDX17/SMAD3/TGIF2

Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, such as the formation of NOTCH1 intracellular domain (NICD1), however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Herein, we revealed that JICD1 induced astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to chemotherapy and radiotherapy. The transcriptome, ChIP-sequencing, and proteomic analyses revealed that JICD1 increased SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. Furthermore, JICD1-driven tumorigenicity was directly regulated by SOX2. Therefore, our results demonstrated that, like NICD1, JICD1 acts as a transcriptional cofactor in the formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

molecular biology↗