Biology subjects

Park, S.-J.

Publications and source records attributed to Park, S.-J..

At least 19 recordsLinked to original sources

bioRxiv2026

A full-length GRAS domain protein underpins efficient shoot regeneration in pepper

Pepper (Capsicum annuum L.) is a recalcitrant species regarding shoot regeneration, a trait that serves as a major bottleneck for the application of genetic engineering tools. In this study, comparative genetic analysis between a rare high-regeneration cultivar and a common low-efficiency cultivar identified a single nucleotide polymorphism (SNP) in PHYTOCHROME A SIGNAL TRANSDUCTION 1 (CaPAT1) that determines shoot regeneration efficiency. The T478C SNP in the high-efficiency cultivar converts a stop codon into an Arg codon, leading to translational read-through into the neighboring gene and forming an intact GRAS domain. This SNP-mediated formation of full-length CaPAT1 is essential for its dimerization. Notably, the overexpression of CaPAT1T478C in multiple low-efficiency cultivars, including both hot and bell peppers, significantly improved both shoot regeneration and transformation efficiency in the transformed T0 generation. These findings demonstrate the pivotal role of CaPAT1 in enhancing shoot regeneration and provide a robust strategy to overcome recalcitrance in pepper.

plant biology↗

bioRxiv2026

HAETAE: A highly accurate and efficient epigenome transformer for tissue-specific histone modification prediction

While genomic models trained on four bases often fail to capture cell-type specificity, we introduce HAETAE, which integrates 5-methylcytosine from long-read sequencing into a 5-base framework. By explicitly modeling epigenetic context, HAETAE achieves state-of-the-art accuracy (>0.95) with orders of magnitude fewer parameters, challenging the prevailing scaling-law paradigm. Furthermore, HAETAE deciphers tissue-specific regulatory logic, as demonstrated by revealing the distinct, context-dependent functional impact of the TERT promoter mutation across diverse tissues.

bioinformatics↗

bioRxiv2025

A deep population stratification and ongoing local adaptations of the range-expanding lovebug Plecia longiforceps

Rapidly range-expanding species provide a superb opportunity to study dynamic demography and ongoing adaptations to novel environments. Plecia longiforceps, a species of lovebug flies native to southeast China and Taiwan, has recently been expanding in Okinawa in Japan and Seoul in South Korea, where massive outbreaks are garnering public attention. Here we analyzed whole-genome sequences of 150 individuals across China, Korea, Okinawa, and Taiwan, including a newly identified northern Chinese population from Qingdao. We found a deep divergence between continental (Korea-China) and insular (Okinawa-Taiwan) populations and specify northern China and Taiwan as sources for Korea and Okinawa, respectively. Severely reduced genetic diversity in Korea and Qingdao suggests serial founder events during their northward expansion. An old split time between Qingdao and Korea ([~]3,500 generations ago) and multiple gene flows into Qingdao reject a simple scenario of a single recent northward migration. Selection signals in northern groups include genes associated with pigmentation, thermal sensing, lipid metabolism, and immunity. We observed a markedly reduced genetic diversity on X chromosome in northern populations, indicating ongoing strong sex-biased selection. Our findings portrait details of the northward range expansion in the species and highlight the role of adaptation for successful invasion at higher latitudes.

evolutionary biology↗

bioRxiv2025

Atelocollagen exhibits superior performance compared to growth factors in upregulating proteins associated with tendon healing

PurposeWe aimed to compare the effects of atelocollagen (AC) and individual growth factors on the expression of key molecular markers associated with tendon healing. MethodsC2C12 myoblasts were cultured in Dulbeccos Modified Eagle Medium (DMEM) containing 5% fetal bovine serum (FBS) and treated with 1 nM or 10 nM of Atelocollagen (AC), bone morphogenetic protein-2 (BMP-2), transforming growth factor-beta 1 (TGF-{beta}1), insulin-like growth factor-1 (IGF-1), or vascular endothelial growth factor (VEGF) for 5 days. After 5 days of treatment, cells were harvested from the culture medium, and Western blot analysis was performed to quantify the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), Collagen type I (Col I), Collagen type III (Col III), and Tenascin C (TnC). Additionally, immunofluorescence staining was conducted to qualitatively assess cytoskeletal organization and cell adhesion, which are key factors in tendon healing. ResultsIn the AC-treated groups, the expression levels of p-ERK, Col I/Col III, and TnC were significantly higher compared to the groups treated with individual growth factors (BMP-2, IGF, VEGF, and TGF-{beta}1) (p < 0.05). These changes were dose-dependent, as there was no significant difference in protein expression between AC and the growth factors at 1 nM, whereas at 10 nM, AC treatment resulted in a significant increase (p < 0.05). In the cell proliferation assay, C2C12 myoblasts treated with AC at 10 nM exhibited significantly higher proliferation rates compared to those treated with individual growth factors (p < 0.05). Additionally, immunofluorescence analysis revealed greater cytoskeletal alignment in AC-treated cells, suggesting enhanced cell adhesion, structural organization, and mechanical stability. ConclusionsAC significantly upregulated key molecular markers involved in cell proliferation, extracellular matrix remodeling, and tendon structural integrity more effectively than individual growth factors. The increased expression of these genes in myoblasts suggests ACs potential role in promoting tendon healing. Clinical relevanceThrough the modulation of key molecular pathways critical to tendon healing, AC presents strong potential as an effective biological augmentation strategy for improving tendon-to-bone interface healing after surgical repair.

cell biology↗

bioRxiv2023

STAIG: Spatial Transcriptomics Analysis via Image-Aided Graph Contrastive Learning for Domain Exploration and Alignment-Free Integration

Spatial transcriptomics is an essential application for investigating cellular structures and interactions and requires multimodal information to precisely study spatial domains. Here, we propose STAIG, a novel deep-learning model that integrates gene expression, spatial coordinates, and histological images using graph-contrastive learning coupled with high-performance feature extraction. STAIG can integrate tissue slices without prealignment and remove batch effects. Moreover, it was designed to accept data acquired from various platforms, with or without histological images. By performing extensive benchmarks, we demonstrated the capability of STAIG to recognize spatial regions with high precision and uncover new insights into tumor microenvironments, highlighting its promising potential in deciphering spatial biological intricates.

bioinformatics↗

bioRxiv2023

HyGAnno: Hybrid graph neural network-based cell type annotation for single-cell ATAC sequencing data

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell ATAC sequencing (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. This calls for novel cell type annotation methods in scATAC-seq, to better explore cell type-specific gene regulatory mechanisms and provide a complementary epigenomic layer to scRNA-seq data. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno integrates genomewide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph that can be used to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was tested using large datasets and demonstrated the advantages of accurate cell annotation, interpretable cell embedding, robustness to noisy reference data, and adaptability to tumor tissues.

bioinformatics↗

bioRxiv2023

A computational approach for deciphering the interactions between proximal and distal regulators in B cell differentiation

Delineating the intricate interplay between promoter-proximal and -distal regulators is crucial for understanding the function of transcriptional mediator complexes implicated in the regulation of gene expression. The aim of the present study was to develop a computational method for accurately modeling the spatial proximal and distal regulatory interactions. Our method combined regression-based models to identify key regulators through gene expression prediction and a graph- embedding approach to detect coregulated genes. This approach enabled a detailed investigation of the gene regulatory mechanisms underlying peripheral B cell differentiation, accompanied by dramatic rearrangements of the genome structure. We found that while the promoter-proximal elements were the principal regulators of gene expression, the distal regulators fine-tuned transcription. Moreover, our approach unveiled the presence of modular regulators, such as structural cofactors and proximal/distal transcriptional factors, which were co-expressed with their target genes. These findings imply that the dysregulation of interactions between transcriptional and structural factors is associated with chromatin reorganization failure and ultimately an increased risk of malignancy. We envisage that our computational approach will help crack the transcriptional cis-regulatory code of the three-dimensional network regulating gene expression.

bioinformatics↗

bioRxiv2023

Multi-omics computational analysis unveils the in-volvement of AP-1 and CTCF in hysteresis of chromatin states during macrophage polarization

Macrophages display extreme plasticity, and the mechanisms and applications of polarization and de/repolarization of macrophages have been extensively investigated. However, the regulation of macrophage hysteresis de/repolarization remains unclear. In this study, by using a large-scale computational analysis of macrophage omics data, we report a list of hysteresis genes that maintain their expression patterns after polarization after ulti- and de/repolarization. While the polarization in M1 macrophages leads to a higher level of hysteresis in genes associated with cell cycle progression, cell migration, and enhancement of the immune response, we found weak levels of hysteresis after M2 polarization. During the polarization process from M0 to M1 and back to M0, the factors IRFs/STAT, AP-1, and CTCF regulate hysteresis by altering their binding sites to the chromatin. Overall, our results show that a history of polarization can lead to hysteresis in gene expression and chromatin changes over a given period. This study contributes to the understanding of de-/repolarization memory in macrophages.

bioinformatics↗

bioRxiv2023

Structural modeling of cytokine-receptor-JAK2 signaling complexes using AlphaFold Multimer

Homodimeric class 1 cytokine receptors include the erythropoietin (EPOR), thrombopoietin (TPOR), granulocyte colony-stimulating factor 3 (CSF3R), growth hormone (GHR), and prolactin receptors (PRLR). They are cell-surface single-pass transmembrane (TM) glycoproteins that regulate cell growth, proliferation, and differentiation and induce oncogenesis. An active TM signaling complex consists of a receptor homodimer, one or two ligands bound to the receptor extracellular domains and two molecules of Janus Kinase 2 (JAK2) constitutively associated with the receptor intracellular domains. Although crystal structures of soluble extracellular domains with ligands have been obtained for all the receptors except TPOR, little is known about the structure and dynamics of the complete TM complexes that activate the downstream JAK-STAT signaling pathway. Three-dimensional models of five human receptor complexes with cytokines and JAK2 were generated using AlphaFold Multimer. Given the large size of the complexes (from 3220 to 4074 residues), the modeling required a stepwise assembly from smaller parts with selection and validation of the models through comparisons with published experimental data. The modeling of active and inactive complexes supports a general activation mechanism that involves ligand binding to a monomeric receptor followed by receptor dimerization and rotational movement of the receptor TM -helices causing proximity, dimerization, and activation of associated JAK2 subunits. The binding mode of two eltrombopag molecules to TM -helices of the active TPOR dimer was proposed. The models also help elucidating the molecular basis of oncogenic mutations that may involve non-canonical activation route. Models equilibrated in explicit lipids of the plasma membrane are publicly available.

biochemistry↗

bioRxiv2023

Rickettsiales' deep evolutionary history sheds light on the emergence of intracellular lifestyles

Ancient bacteria largely lived and flourished as free-living cells till the rise of eukaryotes triggered their adaptation to a new habitat: the intracellular milieu. Rickettsiales bacteria are the most prevalent intracellular microorganisms discovered and the culprits behind some of mankinds worst pestilential diseases. Here, we show that intracellularity is not a defining feature of the group and describe the eco-evolutionary processes that transformed harmless free-living bacteria into obligate intracellular symbionts and parasites. We found that the evolution of free-living lineages towards enhanced cross-feeding interactions with microbial eukaryotes trapped them in a nutritional bind to their trophic partners. We discovered that the oldest Rickettsiales lineages are the closest relatives to modern eukaryotes and are enriched in proteins predicted to have been present in the mitochondrial ancestor. This study not only opens avenues for the detection and surveillance of emerging diseases but also expands our understanding of the origins of complex life. One-Sentence SummaryCross-feeding interactions shaped Rickettsiales genomic architectures along the parasite/free-living spectrum

microbiology↗

bioRxiv2023

MANF stimulates autophagy and restores mitochondrial homeostasis to treat toxic proteinopathy

Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD), one of the leading hereditary kidney diseases, and Alzheimers disease etc. There are no targeted therapies. ADTKD is also a genetic form of renal fibrosis and chronic kidney disease, which affects 500 million people worldwide. For the first time, in our newly generated mouse model recapitulating human ADTKD-UMOD carrying a leading UMOD deletion mutation, we show that autophagy/mitophagy and mitochondrial biogenesis are severely impaired, leading to cGAS- STING activation and tubular injury. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel endoplasmic reticulum stress-regulated secreted protein. We provide the first study that inducible tubular overexpression of MANF after the onset of disease stimulates autophagy/mitophagy and clearance of the misfolded UMOD, and promotes mitochondrial biogenesis through p-AMPK enhancement, resulting in protection of kidney function. Conversely, genetic ablation of endogenous MANF upregulated in the mutant mouse and human tubular cells worsens autophagy suppression and kidney fibrosis. Together, we discover MANF as a novel biotherapeutic protein and elucidate previously unknown mechanisms of MANF in regulating organelle homeostasis to treat ADTKD, which may have broad therapeutic application to treat various proteinopathies.

cell biology↗

bioRxiv2022

Genetic diversity assessment of Pacific oyster Magallana gigas (Crassostrea gigas) populations from the two southern coastal farms in South Korea

South Korea is among the major producers of the Pacific oyster, Magallana gigas (Crassostrea gigas), which is one of the most valued aquaculture species. Since the early 1990s, climatic and anthropogenic factors have incurred the reduction of their wild seeds, whereby the dependence on hatchery-produced seeds has constantly increased in South Korea, thus raising concerns about losing genetic diversity and accelerating genetic deterioration. To better understand their genetic make-up, we assessed the genetic diversity of M. gigas populations from two farms (Tongyeong and Gadeokdo) in the southern coast, where about 80% of the cultivated oysters in Korea are produced. Tongyeong showed slightly higher diversity than Gadeokdo, but both populations had a similar genetic structure characterized by low nucleotide diversity. Comparative haplotype analyses provided data supporting unique genetic features of the populations that include (1) weak genotype-locality relationship, (2) low levels of gene flow between populations, and (3) seasonal fluctuation of genetic variation within a population. Furthermore, the highly alike haplotype network patterns were observed between the wild and farm populations as well as among the populations in neighboring countries, which suggests that the genetic structure is conserved between wild and hatchery populations, and geographic proximity has minimal influence on the genetic composition. These results warrant further study in biological and ecological contexts and will be invaluable in formulating genetic monitoring and sustainable long-term management of M. gigas.

genetics↗

bioRxiv2022

Gut microbiota analysis of the western honeybee (Apis mellifera L.) infested with the mite Varroa destructor reveals altered bacterial and archaeal community

The western honeybee, Apis mellifera L., is a crop pollinator that makes royal jelly and other hive products. However, widespread concerns arise about opportunistic diseases (e.g., bacteria, fungi, or mites) or chemicals that have an effect on the health and number of colonies, as well as their activity. The relationships between the gut microbiota and its host are currently being researched extensively. The effects of Varroa destructor infection on the gut microbial community, in particular, have received little investigation. This work utilized amplicon sequencing of the bacterial and archaeal 16S rRNA genes to assess the bacterial and archaeal communities of adult bee groups (healthy and affected by Varroa designed in NG and VG, respectively) and larvae from Varroa destructor-infected hives. Our results suggest that the genus Bombella was substantially dominant in larvae, while the genera Gillamella, unidentified Lactobacillaceae, and Snodgrassella were significantly dominant in adult bees. NG and VG, on the other hand, did not differ statistically significantly. The PICRUSt study revealed a significant difference in the KEGG classifications of larvae and adult bee groups. A greater number of genes involved in cofactor and vitamin production were identified in larvae. Additionally, despite the complexity of the honeybees bacterial community, all groups exhibited a straightforward archaeal community structure. Surprisingly, methanogen was detected in low abundance in the microbiota of honeybees. In summary, larvae and adult bees infected with Varroa destructor exhibit altered gut microbiota composition and function.

microbiology↗

bioRxiv2021

Dynamic Interactions of Fully Glycosylated SARS-CoV-2 Spike Protein with Various Antibodies

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a public health crisis, and the vaccines that can induce highly potent neutralizing antibodies are essential for ending the pandemic. The spike (S) protein on the viral envelope mediates human angiotensin-converting enzyme 2 (ACE2) binding and thus is the target of a variety of neutralizing antibodies. In this work, we built various S trimer-antibody complex structures on the basis of the fully glycosylated S protein models described in our previous work, and performed all-atom molecular dynamics simulations to get insight into the structural dynamics and interactions between S protein and antibodies. Investigation of the residues critical for S-antibody binding allows us to predict the potential influence of mutations in SARS-CoV-2 variants. Comparison of the glycan conformations between S-only and S-antibody systems reveals the roles of glycans in S-antibody binding. In addition, we explored the antibody binding modes, and the influences of antibody on the motion of S protein receptor binding domains. Overall, our analyses provide a better understanding of S-antibody interactions, and the simulation-based S-antibody interaction maps could be used to predict the influences of S mutation on S-antibody interactions, which will be useful for the development of vaccine and antibody-based therapy.

biophysics↗

bioRxiv2021

Nanoparticle Cellular Internalization is Not Required for RNA Delivery to Mature Plant Leaves

Rapidly growing interest in nanoparticle-mediated delivery of DNA and RNA to plants requires a better understanding of how nanoparticles and their cargoes translocate in plant tissues and into plant cells. However, little is known about how the size and shape of nanoparticles influences transport in plants and use of their cargoes, limiting development and deployment of nanotechnology in plant systems. Here, we employ non-biolistically delivered DNA-modified gold nanoparticles (AuNP) spanning various sizes (5 - 20 nm) and shapes (spheres and rods) to systematically investigate their transport following infiltration into Nicotiana benthamiana (Nb) leaves. Generally, smaller AuNPs demonstrate more rapid, higher, and longer-lasting levels of association with plant cell walls compared to larger AuNPs. We observe internalization of rod-shaped but not spherical AuNPs into plant cells, yet surprisingly, 10 nm spherical AuNP functionalized with small-interfering RNA (siRNA) are most efficient at siRNA delivery and inducing gene silencing in mature plant leaves. These results indicate the importance of nanoparticle size in efficient biomolecule delivery, and, counterintuitively, demonstrate that efficient cargo delivery is possible and potentially optimal in the absence of nanoparticle cellular internalization. Our results highlight nanoparticle features of importance for transport within plant tissues, providing a mechanistic overview of how nanoparticles can be designed to achieve efficacious bio-cargo delivery for future developments in plant nanobiotechnology.

bioengineering↗

bioRxiv2020

Efficient GNE myopathy disease modeling with mutation specific phenotypes in human pluripotent stem cells by base editors

Despite the great potential of disease modeling with the isogenic pairs of human pluripotent stem cells (hPSCs), the extremely low efficiency of precise gene editing in hPSCs remains a technical hurdle for this approach. Herein, we took advantage of currently available base editors (BEs) to epitomize the isogenic disease model from hPSCs. Using this method, we established 14 hPSCs that harbor point mutations on the GNE gene, including four different mutations found in GNE myopathy patients. Due to lesser activation of p53 by BEs than Cas9, a higher editing efficiency with BEs was achieved. Four different mutations in the epimerase or kinase domains of GNE revealed mutation-specific hyposialylation, which was closely correlated to pathological clinical phenotypes. These mutation-specific hyposialylation patterns were evident in GNE protein structure modeling. Furthermore, treatment with a drug candidate currently under clinical trials showed a mutation-specific drug response in GNE myopathy disease models. These data suggest that isogenic disease models from hPSCs using BEs could serve as a useful tool for mimicking the pathophysiology of GNE myopathy and for predicting drug responses.

developmental biology↗

bioRxiv2020

Single-cell Transcriptome of Bronchoalveolar Lavage Fluid Reveals Dynamic Change of Macrophages During SARS-CoV-2 Infection in Ferrets

Although the profile of immune cells changes during the natural course of SARS-CoV-2 inflection in human patients, few studies have used a longitudinal approach to reveal their dynamic features. Here, we performed single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment showed dynamic changes in cell proportions and characteristics in uninfected control, at 2 days post-infection (dpi) (early stage of SARS-CoV-2 infection with peak viral titer), and 5 dpi (resolution phase). NK cells and CD8+ T cells exhibited activated subclusters with interferon-stimulated features, which were peaked at 2 dpi. Intriguingly, macrophages were classified into 10 distinct subpopulations, and their relative proportions changed over the time. We observed prominent transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, especially at 2 dpi. Moreover, trajectory analysis revealed gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identified the distinct macrophage subpopulation that had rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we found that different spectrums of M1 or M2 macrophages showed distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.

immunology↗

bioRxiv2020

Structure, Dynamics, Receptor Binding, and Antibody Binding of Fully-glycosylated Full-length SARS-CoV-2 Spike Protein in a Viral Membrane

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates host cell entry by binding to angiotensin-converting enzyme 2 (ACE2), and is considered the major target for drug and vaccine development. We previously built fully-glycosylated full-length SARS-CoV-2 S protein models in a viral membrane including both open and closed conformations of receptor binding domain (RBD) and different templates for the stalk region. In this work, multiple s-long all-atom molecular dynamics simulations were performed to provide deeper insight into the structure and dynamics of S protein, and glycan functions. Our simulations reveal that the highly flexible stalk is composed of two independent joints and most probable S protein orientations are competent for ACE2 binding. We identify multiple glycans stabilizing the open and/or closed states of RBD, and demonstrate that the exposure of antibody epitopes can be captured by detailed antibody-glycan clash analysis instead of a commonly-used accessible surface area analysis that tends to overestimate the impact of glycan shielding and neglect possible detailed interactions between glycan and antibody. Overall, our observations offer structural and dynamic insight into SARS-CoV-2 S protein and potentialize for guiding the design of effective antiviral therapeutics.

biophysics↗