Biology subjects

Choi, Y. H.

Publications and source records attributed to Choi, Y. H..

11 recordsLinked to original sources

bioRxiv2026

Acetyl-CoA availability regulates neuronal metabolism, growth, and synaptic activity

The metabolite acetyl-CoA plays a central role in cellular metabolic homeostasis. As part of the secretory pathway, acetyl-CoA is imported into the endoplasmic reticulum (ER) by a membrane-bound transporter AT-1 (SLC33A1). AT-1 has been linked to peripheral neuropathy (heterozygous mutations), developmental delay with premature death (homozygous mutations) and intellectual disability with progeria (duplication). These phenotypes can be reproduced in the mouse. Here, we show that AT-1 overexpression in primary neurons impacts diverse phenotypes related to neuronal function and plasticity. At the gene level, AT-1 induces brain aging signatures, and key differences in ribosomal and synaptic processes were identified in both the transcriptome and the proteome. Changes in mitochondria-associated pathways were reflected in an increase in expression of mitochondrial master regulator PGC-1 and its target genes. Functionally, marked differences in mitochondrial membrane potential, architecture, and respiration were detected. Tracing experiments indicated altered glucose utilization in glycogen storage and nucleotide production. Shifts in redox metabolism were linked to differences in levels of NAD-dependent SIRT1 and CtBP2, with consequences for acetylated lysine modification. Depletion of lipid stores was associated with greater plasticity in fuel substrate utilization and a major shift in cellular lipid composition. These broad-scale changes in metabolism were coincident with reduced expression of synaptic proteins and reduced activity among synaptic networks, indicating that neuronal electrophysiology and network communication are coordinated at least in part through neuronal acetyl-CoA metabolism.

cell biology↗

bioRxiv2025

ETV4 restrains the formation of CD74+ cytotoxic exhausted CD8+ T cells

Exhausted CD8+ T (Tex) cells comprise heterogeneous subsets with varying cytotoxic and dysfunctional properties, making inhibitory receptor profiles unreliable indicators of function. Therefore, it is essential to define transcriptional regulators or markers that accurately reflect these states. Here, we identified ETS variant 4 (ETV4) as a transcription factor that restricts cytotoxic Tex differentiation within tumors. ETV4 deficiency promotes the emergence of a CD74+ cytotoxic Tex subset while preserving the progenitor Tex (Tpex) pool. CD74 serves as both a marker and regulator, reinforcing Tpex features and enhancing Tex cytotoxicity. Mechanistically, ETV4 loss derepresses T-bet expression, thereby increasing IFN{gamma} production that induces CD74 expression in a paracrine manner. Single-cell analyses across human cancers revealed that CD74+ Tex cells are enriched for proliferative and metabolic programs and correlate with improved survival. Collectively, we establish the ETV4-CD74 axis as a regulator of Tex fate and promising therapeutic target to augment anti-tumor immunity.

immunology↗

bioRxiv2025

NADES as Biocompatible Media for Thermally Stable RNA Molecules

The inherently low thermal stability of RNA poses operational, accessibility, and financial challenges for RNA research and RNA-based technologies. Natural deep eutectic solvents (NADES) have been shown to enhance the stability of various macromolecules, including DNA and protein. This study explores NADES as alternative storage media for RNA preservation and evaluates their biocompatibility in human cells. In vitro-transcribed mRNA was stored in various NADES at temperatures ranging from 4-50 {degrees}C, and the integrity was assessed by quantifying its translatability, represented by protein-expressing cells. NADES effectively preserved RNA integrity, retaining over 50% of its translatability for at least four months at room temperature (21 {degrees}C) and 48 hours at 50 {degrees}C, in comparison to -80 {degrees}C storage. Notably, the preservation efficacy remained unaffected by temperature fluctuations. Furthermore, the selected NADES concentrations maintained [~] 99% cell viability, demonstrating their biocompatibility. These findings establish NADES as efficient, biocompatible RNA storage media, enabling stable storage and transport at ambient and extreme temperatures while withstanding sudden fluctuations. This enhanced stability simplifies and expands the accessibility of RNA-based applications. Additionally, the biocompatibility of NADES supports their potential use in RNA-based biomedical applications.

pharmacology and toxicology↗

bioRxiv2025

Adaptive strategies of Caribbean sponge holobionts beyond the mesophotic zone

Marine sponges and their microbiomes function together as holobionts, playing essential roles in ecosystem dynamics and exhibiting remarkable adaptability across depth gradients. This study utilized a multi-omics approach, integrating microbiome and metabolome analyses, to investigate adaptive strategies in sponge holobionts inhabiting the mesophotic (80-125 m), upper-rariphotic (125-200 m), and lower-rariphotic (200-305 m) zones of Curacao. We hypothesized that depth-related environmental factors drive distinct adaptive strategies, similar to patterns observed in fish and coral assemblages. Results revealed major differences in holometabolomes and microbial communities between Demospongiae and Hexactinellida sponges, reflecting class-specific adaptive strategies. Notably, phospholipid homeoviscous adaptation to temperature and pressure emerged as a key mechanism in phosphorus metabolism. Adaptations in nitrogen metabolism were linked to diverse ammonia oxidizing archaea (AOA) symbionts, and dissolved organic matter cycling. Hexactinellid microbiomes exhibited intra-specific heterogeneity; however, species-specific associations with AOA symbionts such as Cenarchaeum and Nitrosopumilus were observed. Additionally, the lower-rariphotic hexactinellid holometabolomes highlighted the significance of the nested ecosystem concept through the identification of secondary metabolites produced by their associated fauna (aphrocallistins by zoanthids, and xanthurenic acid by shrimp). This study highlights the ecological significance of sponge holobionts in mesophotic and rariphotic ecosystems, revealing diverse adaptations to unique physicochemical conditions and biotic interactions.

microbiology↗

bioRxiv2025

Blue Light Sonata: Dynamic variation of red:blue ratio during the photoperiod differentially affects leaf photosynthesis, pigments, and growth in lettuce

Vertical farming (VF) has unparalleled capacity to highly customize plant growth environments. In VF, red and blue LED lights are predominantly used as the two main wavelengths for photosynthesis. For many plants, red light increases biomass, and blue light can increase nutritional content. Because red light is more cost-and energy-efficient to produce than blue light, refined growth recipes are imperative to mutualistically improve efficiency with crop yield and quality. This studys aim was to balance lighting energy-use with growth and nutritional quality by using "dynamic lighting" recipes to reduce durations of high-intensity blue light. Lettuce (Lactuca sativa L.) was grown for 21 days at 220 mol m-2 s-1, receiving one of five R:B ratios (R:B100:0, R:B95:5, R:B89:11, R:B50:50, and R:B0:100) for either the whole 18-hour photoperiod (Whole Day), the first six hours of the photoperiod (Morning), or the last six hours of the photoperiod (Evening). Morning and Evening treatments received low blue (R:B89:11) for the remaining 12 hours of the day. The Morning and Evening high blue treatments had greater fresh weight and leaf area than their respective Whole Day treatments, attributed to reduced instantaneous leaf photosynthesis under high blue. High blue reduced photosynthesis during only the six hours of Morning and Evening treatments, compared to the full impact of static high blue for 18-hour Whole Day treatments. Intriguingly, with only six hours of R:B0:100, Morning and Evening treatments had the same high anthocyanin content as lettuce grown for 18 hours under R:B0:100. Therefore, daily blue light fraction can be reduced by using dynamic treatments to more efficiently promote growth and nutritional quality.

plant biology↗

bioRxiv2023

Dual role of Vascular Endothelial Growth Factor-C (VEGF-C) in post-stroke recovery

Using a mouse model of ischemic stroke, this study characterizes stroke-induced lymphangiogenesis at the cribriform plate (CP). While blocking CP lymphangiogenesis with a VEGFR-3 inhibitor improves stroke outcome, administration of VEGF-C induced larger brain infarcts. AbstractCerebrospinal fluid (CSF), antigens, and antigen-presenting cells drain from the central nervous system (CNS) into lymphatic vessels near the cribriform plate and dural meningeal lymphatics. However, the pathological roles of these lymphatic vessels surrounding the CNS during stroke are not well understood. Using a mouse model of ischemic stroke, transient middle cerebral artery occlusion (tMCAO), we show that stroke induces lymphangiogenesis near the cribriform plate. Interestingly, lymphangiogenesis is restricted to lymphatic vessels at the cribriform plate and downstream cervical lymph nodes, without affecting the conserved network of lymphatic vessels in the dura. Cribriform plate lymphangiogenesis peaks at day 7 and regresses by day 14 following tMCAO and is regulated by VEGF-C/VEGFR-3. These newly developed lymphangiogenic vessels transport CSF and immune cells to the cervical lymph nodes. Inhibition of VEGF-C/VEGFR-3 signaling using a blocker of VEGFR-3 prevented lymphangiogenesis and led to improved stroke outcomes at earlier time points but had no effects at later time points following stroke. Administration of VEGF-C after tMCAO did not further increase post-stroke lymphangiogenesis, but instead induced larger brain infarcts. The differential roles for VEGFR-3 inhibition and VEGF-C in regulating stroke pathology call into question recent suggestions to use VEGF-C therapeutically for stroke.

immunology↗

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↗

bioRxiv2021

Sequence grammar underlying unfolding and phase separation of globular proteins

Aberrant phase separation of globular proteins is associated with many diseases. Here, we use a model protein system to understand how unfolded states of globular proteins drive phase separation and the formation of unfolded protein deposits (UPODs). For UPODs to form, the concentrations of unfolded molecules must be above a threshold value. Additionally, unfolded molecules must possess appropriate sequence grammars to drive phase separation. While UPODs recruit molecular chaperones, their compositional profiles are also influenced by synergistic physicochemical interactions governed by the sequence grammars of unfolded proteins and sequence features of cellular proteins. Overall, we find that the driving forces for phase separation and the compositional profiles of UPODs are governed by the sequence grammar of unfolded proteins. Our studies highlight the need for uncovering the sequence grammars of unfolded proteins that drive UPOD formation and lead to gain-of-function interactions whereby proteins are aberrantly recruited into UPODs. HighlightsO_LIUnfolded states of globular proteins phase separate to form UPODs in cells C_LIO_LIThe fraction of unfolded molecules and the sticker grammar govern phase separation C_LIO_LIHydrophobic residues act as stickers that engage in intermolecular interactions C_LIO_LISticker grammar also influences gain-of-function recruitment into aberrant UPODs C_LI

biophysics↗

bioRxiv2020

Neuroinflammation alters the phenotype of lymphangiogenic vessels near the cribriform plate.

Meningeal lymphatic vessels residing in the dural layer surrounding the dorsal regions of the brain, basal regions, and near the cribriform plate have all been implicated in the management of neuroinflammation and edema. Interestingly, only the lymphatic vessels near the cribriform plate undergo functional lymphangiogenesis in a mouse model of Multiple Sclerosis, suggesting these particular lymphatics uniquely undergo dynamic changes in response to neuroinflammation and may have distinct access to pro-lymphangiogenic factors in the CNS. However, it is unknown if these newly formed lymphangiogenic vessels are functionally similar to steady-state or if they have any other functional changes during neuroinflammation. In this study, we generated a novel protocol to isolate lymphatic endothelial cells from the cribriform plate for single cell analysis. We demonstrate that neuroinflammation-induced lymphangiogenic vessels undergo unique changes, including the capture of CNS-derived antigens, upregulation of adhesion and immune-modulatory molecules to interact with dendritic cells, and display IFN-{gamma} dependent changes in response to the microenvironment. Single-cell trajectory analysis showed that cribriform plate lymphangiogenic vessels are post-proliferative and not generated from trans-differentiation of myeloid cells. Additionally, we show that these lymphangiogenic vessels have access to a CSF reservoir, express the water pore Aquaporin-1, and may have direct access to the CSF due to gaps in the arachnoid epithelial layer separating the dura from the subarachnoid space. These data characterize cribriform plate lymphatics and demonstrate that these vessels are dynamic structures that engage in leukocyte interactions, antigen sampling, and undergo expansion to drain excess fluid during neuroinflammation. Neuroinflammation not only induces efficient drainage of CSF but also alters the functions of lymphatic vessels near the cribriform plate.

immunology↗

bioRxiv2020

The instantaneous multi-pronged defense system of latex against general plant enemies

Based on the hypothesis that variation of the metabolomes of latex is a response to selective pressure and should thus be affected differently from other organs, their variation could provide insight into the defensive chemical selection of plants. Metabolic profiling was utilized to compare tissues of Euphorbia species collected in various regions. The metabolic variation of latexes was much more limited than that of other organs. In all of the species, the levels of polyisoprenes and terpenoids were found to be much higher in latexes than in leaves and roots. Polyisoprenes were also observed to physically delay the contact and growth of pathogens with plant tissues. A secondary barrier composed of terpenes and, in particular, 24-methylenecycloartanol, exhibited antifungal activity. These results, together with the known roles of the enzymes also present in latexes, demonstrate that they are part of a cooperative defense system that comprises both biochemical and physical elements.

ecology↗

bioRxiv2019

Antibiotic production is organized by a division of labour in Streptomyces

One of the hallmark behaviors of social groups is division of labour, where different group members become specialized to carry out complementary tasks. By dividing labour, cooperative groups of individuals increase their efficiency, thereby raising group fitness even if these specialized behaviors reduce the fitness of individual group members. Here we provide evidence that antibiotic production in colonies of the multicellular bacterium Streptomyces coelicolor is coordinated by a division of labour. We show that S. coelicolor colonies are genetically heterogenous due to massive amplifications and deletions to the chromosome. Cells with gross chromosomal changes produce an increased diversity of secondary metabolites and secrete significantly more antibiotics; however, these changes come at the cost of dramatically reduced individual fitness, providing direct evidence for a trade-off between secondary metabolite production and fitness. Finally, we show that colonies containing mixtures of mutant strains and their parents produce significantly more antibiotics, while colony-wide spore production remains unchanged. Our work demonstrates that by generating mutants that are specialized to hyper-produce antibiotics, streptomycetes reduce the colony-wide fitness costs of secreted secondary metabolites while maximizing the yield and diversity of these products.

evolutionary biology↗