Biology subjects

Jeong, H.

Publications and source records attributed to Jeong, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Imbalance between RNA-binding proteins and the WAVE regulatory complex underlies the toxic gain-of-function effects of the CYFIP2 Arg87Cys variant in neurodevelopmental disorders

Pathogenic variants in cytoplasmic FMR1-interacting protein 2 (CYFIP2) cause neurodevelopmental disorders, with hotspot substitutions at arginine 87 (Arg87) associated with particularly severe symptoms. CYFIP2 functions both as a component of the WAVE (Wiskott-Aldrich syndrome protein family verprolin-homologous protein) regulatory complex (WRC), regulating the actin cytoskeleton, and as an interactor of RNA-binding proteins (RBPs) involved in mRNA processing/translation. Although Arg87 variants reduce CYFIP2 protein stability, heterozygous knock-in mice carrying Arg87Cys (Cyfip2+/R87C) show markedly more severe phenotypes than heterozygous knockout (Cyfip2+/-) mice, supporting a toxic gain-of-function mechanism. However, how the dual roles of CYFIP2 contribute to this mechanism remains unclear. To address this, we examined Cyfip2+/R87C mice at postnatal week 7, before overt neuronal loss and gliosis, focusing on the progressive dispersion of hippocampal cornu ammonis 1 (CA1) pyramidal neurons, a phenotype absent in Cyfip2+/- mice. Single-nucleus RNA sequencing suggested candidate alterations related to translation and cell adhesion/migration in CA1 pyramidal neurons. Complementarily, human embryonic kidney 293T cells expressing CYFIP2 Arg87Cys showed defects in proliferation and morphology, accompanied by altered expression of cell adhesion-related genes. Quantitative proteomic analysis of the CA1 region uncovered an imbalance between CYFIP2-associated protein networks, characterized by increased RBPs and reduced WRC components. Phosphoproteomic analysis further revealed altered phosphorylation of synaptic and translational regulators. Consistently, whole-cell recordings and biocytin-based morphological analyses showed increased frequency of miniature excitatory postsynaptic currents and altered dendritic morphology in Cyfip2+/R87C CA1 pyramidal neurons, most prominently in the more severely dispersed deep-layer neurons. Moreover, the cell adhesion molecule Eph receptor A3 was reduced, possibly as a result of RBP dysregulation. Together, these findings suggest that an imbalance between RBP- and WRC-associated pathways underlies the gain-of-function effects of CYFIP2 Arg87Cys and contributes to early neuronal phenotypes, most notably CA1 layer dispersion. This mechanism, distinct from CYFIP2 haploinsufficiency, supports allele-specific therapeutic strategies for Arg87 variants.

neuroscience↗

bioRxiv2026

The role of world knowledge in sentence comprehension under working-memory constraints: An fMRI study

Introduction: Comprehension of thematic roles, i.e., "who did what to whom," relies on limited cognitive resources, and constraints on these resources can alter the use of plausibility information derived from world knowledge. Although sentence-processing studies have described how plausibility information constrains interpretation, it remains unclear how this process is supported by the architecture of working memory. This study examines whether the phonological loop, one of the components of working memory, contributes to thematic-role processing based on world knowledge. Methods: Using articulatory suppression and functional magnetic resonance imaging, we examined whether constraining the function of the phonological loop modulates behavioral and neural responses to sentences in which syntactically assigned thematic roles are plausible or implausible given world knowledge. To constrain the phonological loop, we manipulated the task: a single task and a dual task involving concurrent articulation. Results: We found no significant interaction between task and plausibility, although equivalence analyses did not provide evidence for the absence of a plausibility effect during articulation. In contrast, a robust main effect of thematic-role plausibility was observed: implausible sentences elicited greater activation than plausible sentences in the left inferior frontal gyrus (LIFG) and medial superior frontal gyrus (mSFG) at the whole-brain level, and in both the pars triangularis and pars orbitalis of the LIFG in the ROI analyses. Discussion: These findings provide no conclusive evidence that constraining the phonological loop substantially modulates the use of world knowledge in comprehension of thematic roles, while also leaving open the possibility of a smaller task-dependent effect. At the same time, the robust neural responses to implausibility indicate that the LIFG and mSFG consistently contribute to the processing of plausibility information derived from world knowledge.

neuroscience↗

bioRxiv2026

Resource-access breadth marks protective strains against toxigenic Clostridioides difficile

Antibiotic disruption of gut microbiota creates opportunities for toxigenic Clostridioides difficile. One strategy is to occupy this niche with a non-toxigenic or weakly virulent strain, but even strains that cause little disease may fail to compete during pathogen challenge. We screened 21 sequence type 1 (ST1) isolates for their ability to protect mice co-colonized with toxigenic VPI10463, separating disease potential from protection. Some strains, such as ST1-75, caused little disease and protected, whereas others, such as ST1-68, caused little disease but failed to protect. Metabolomics showed that ST1-75 depleted more proline than ST1-68, whereas another protective strain, ST1-6, had a different metabolic profile; both protective strains nevertheless responded to many substrates. Substrate-utilization profiling revealed that protection across the 21 isolates correlated with amino-acid overlap with VPI10463, but not overall nutrient overlap or shared genome-encoded protein families. Relative amino-acid access explained variation beyond mono-colonization disease potential, and a consumer-resource model showed how nutrient overlap together with additional resource access can support persistence during competition. Additional experiments support that ST1-mediated protection occurs even in the absence of mature B and T cells. These findings distinguish low disease potential from protection, link protection to strain competition, and identify relative resource access as an informative phenotype for prioritizing strains for biotherapeutic testing.

microbiology↗

bioRxiv2026

High-SNR Whole-Brain Mesoscale Diffusion MRI Using Rotating-View Acquisitions (ROVER-dMRI)

Purpose: We aim to acquire and reconstruct high signal-to-noise ratio (SNR), whole-brain, mesoscale (isotropic submillimeter) diffusion MRI (dMRI) in vivo in a clinically feasible scan time. Methods: We present ROVER-dMRI, a unified rotating-view acquisition and super-resolution reconstruction framework. Thick slices (up to 10 mm)acquired across many rotated orientations improve the base SNR, and a shared multi-resolution hash-encoded implicit neural representation (INR) with per-direction MLP head and a physics-informed, Bloch-simulated slice-profile forward model reconstructs these views into a continuous isotropic volume (up to 13x super-resolution) in a self-supervised manner. ROVER-dMRI was evaluated in vivo on human brain (0.78 mm isotropic and 0.5 mm isotropic) and monkey brain (0.6 mm isotropic) across MRI platforms with varying gradient performance, and benchmarked against gSlider-SMS and least-squares super-resolution reconstruction (LS-SRR). Results: At 0.78 mm isotropic resolution, ROVER-dMRI diffusion- weighted images achieved higher SNR than the vendor product sequence, whose images were limited by the noise floor, while its directionally encoded color (DEC) maps showed lower noise than gSlider. When reducing the number of views from 20 to 13 (reducing the scan time by 65% ), ROVER-dMRI acquisition/reconstruction preserved all fine details in the fiber orientations. In the monkey brain, its DEC map matched a 60-direction gSlider acquisition at only 40% of the scan time. ROVER-dMRI preserved coherent fiber-orientation-distribution (FOD) structure, including crossing fibers, and recovered fine details in the cerebellum at 0.5 mm isotropic, that are not visible at 0.78 mm resolution. Compared to state-of- the-art 0.5 mm methods, ROVER-dMRI reduced scan time by 73% while acquiring more diffusion directions. Conclusion: ROVER-dMRI offers a practical route to high-SNR whole-brain mesoscale diffusion imaging in vivo, with the pulse sequence and reconstruction pipeline released as open source. KEYWORDS: diffusion MRI, super-resolution, implicit neural representation, hash encoding, physics informed learning

neuroscience↗

bioRxiv2026

Divergent Dopamine Dynamics within the Accumbens Core

Dopamine in the nucleus accumbens Core powerfully influences motivation and learning, yet the information encoded by Core dopamine remains unresolved. Competing theories typically assume a spatially uniform signal, and standard recording methods average dopamine over substantial tissue volumes. Using two-photon imaging through microprisms in behaving mice, we reveal a pronounced spatial organization of Core dopamine dynamics. Posterior Core showed phasic dopamine increases to both rewards and aversive stimuli, with transfer to a predictive cue after learning. Anterior Core showed phasic decreases to aversive stimuli, weaker increases to reward, and higher tonic dopamine that was further amplified by cocaine. Rather than uniform or highly fragmented signals, the Core contains a smoothly graded mixture between two distinct sets of dopamine dynamics, neither matching canonical reward prediction errors.

neuroscience↗

bioRxiv2026

Inherited proliferation states organize plant transcriptomes

A central question in plant biology is whether natural transcriptome variation primarily reflects environmental adaptation or intrinsic genetic programs. Using transcriptomes from 665 natural Arabidopsis thaliana accessions, we show that inherited population structure, not environmental gradients, is the primary organizer of global transcriptome architecture. Genomic population structure uniquely explains 30.0% of transcriptome-wide variation, while environmental variables account for only 2.5%. This architecture is dominated by a single co-expression program (proliferation Module Eigengene: prolifME), enriched for cell cycle regulation and ribosome biogenesis, regulated by a bipartite transcription factor architecture, and genetically encoded at discrete loci with broad trans-regulatory effects. This proliferation program is associated with reduced plant size, biomass, growth rate and water-use efficiency, and these relationships persist under common-garden conditions. Gene contributions to this proliferation program are non-randomly conserved in rice and maize across 150-200 million years of divergence. These findings identify an intrinsic transcriptional proliferation program as a primary state of plant population transcriptomes, conserved across plant species.

plant biology↗

bioRxiv2026

BCCWJ-Brain: A Multi-Modal fMRI, MEG, and EEG Dataset of Naturalistic Japanese Reading

We present the BCCWJ-Brain dataset, a multi-modal neuroimaging resource comprising functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and electroencephalography (EEG) data recorded from native Japanese speakers reading newspaper articles from the Balanced Corpus of Contemporary Written Japanese (BCCWJ). Neural data were collected from 112 participants (36 fMRI, 35 MEG, and 41 EEG) as they read twenty newspaper articles presented in a Rapid Serial Visual Presentation (RSVP) paradigm. By providing three complementary neuroimaging modalities collected under identical naturalistic reading stimuli, this dataset provides a cognitive benchmark for computational models such as large language models. The dataset is publicly available on the OpenNeuro platform, offering a valuable resource for neuroscience, natural language processing, and related research fields.

neuroscience↗

bioRxiv2026

Germline hypomethylation shapes dynamic CpG reservoirs in ape genomes

Telomere-to-telomere (T2T) genome assemblies resolve DNA methylation of complete ape genomes, including repetitive and satellite-rich compartments that were largely inaccessible in previous primate reference genomes. Here, integrating complete ape genome assemblies with long- and short-read germline and somatic DNA methylomes, we demonstrate dual roles of germline DNA methylation. While solidifying germline DNA methylation as a major driver of genome-wide long-term CpG erosion, we report an unexpected reservoir of hypomethylated CpGs that exist in previously inaccessible regions. Specifically, peri/centromeric satellites are markedly hypomethylated in sperm across great apes, despite their heterochromatic context and rapid sequence turnover. Moreover, we found their hypomethylation extends into adjacent non-satellite DNA at the boundaries of satellite-rich heterochromatic sequences and adjacent euchromatic sequences, forming centromeric hypomethylated extension domains, or CHEDs. CHEDs are enriched in recently duplicated genes, and CHED-associated genes show reproducible, enriched expression in the brain and testis. Extending our analyses to other structurally dynamic regions, including lineage-specific insertions, recent segmental duplications and structurally divergent regions, we show that these regions are also CpG-rich and relatively hypomethylated in sperm. Together, our results reveal a unique germline hypomethylation landscape in ape genomes in which structurally dynamic regions act not only as substrates of rapid genome evolution, but also as transient reservoirs of CpG-rich sequence contexts, promoting evolutionary innovations involving new genes and tissue-biased expression.

genomics↗

bioRxiv2026

Label-Free All-Electrical Tracking of Individual and Collective Cell Migration on a Megapixel CMOS Capacitance Sensor

Label-free tracking of adherent cell migration could enable important insights into biological processes such as tissue repair, inflammatory response, or cancer progression. Nevertheless, visualizing unlabeled animal cells using optical microscopy remains challenging due to low contrast as well as frequent changes in cell shape and number. A promising alternative uses electrical capacitance measurements, which are sensitive to cell adhesion to electrode surfaces. However, prior examples often utilized electrodes with areas larger than single cells, resulting in averaged readouts over multiple cells. Here, we demonstrate label-free, live-cell tracking using a capacitance sensor array with more than 1 million pixels on a 10 micron pitch across an area larger than 1 square centimeter. We show that single cell morphology can be clearly segmented, and then used to reconstruct migration and proliferation dynamics using optical flow. We further track the spreading of multicellular spheroids, revealing fast-moving peripheral regions led by a collective leader cell "front." Finally, we demonstrate label-free imaging of millimeter-scale honeycomb-shaped tissues without the multi-image stitching often required for conventional microscopy. We utilize mutual capacitance measurements with electrically-programmable electrode spacing to reconstruct topographical features of these engineered tissues. Overall, CMOS capacitance imaging arrays enables label-free imaging spanning from single cells to large tissues, in a portable and scalable format for settings where optical microscopy may be difficult to access.

bioengineering↗

bioRxiv2026

The toll-like receptor signalling pathway is altered in iPSC-derived cortical networks from people with bipolar disorder.

BackgroundInduced pluripotent stem cell (iPSC)-derived brain cells are widely utilized as in vitro models for several neuropsychiatric disorders, as they retain the donors genetic profile, offering a unique opportunity to study living human brain cells and perform controlled experimental manipulations. In this study, we conducted whole transcriptome sequencing of cortical networks (co-cultures of neurons and astrocytes) derived from 12 participants with bipolar disorder (BD) and 12 participants without a history of mental health disorders. We aimed to identify new molecular mechanisms underlying the pathophysiology of bipolar disorder. MethodsiPSCs were generated by reprogramming peripheral blood mononuclear cells using episomal vectors. They were then differentiated into neural progenitor cells and matured into cortical networks that express markers of neurons and astrocytes. Whole transcriptome data were obtained using the Illumina NovaSeq X sequencing platform. ResultsDifferential expression analysis was performed using DESeq2 in R, and the identified genes were used for gene set enrichment analysis, which identified 191 enriched pathways in BD. Of these, the toll-like signalling pathway, which is downregulated in BD, was further investigated. ConclusionOur results suggest a profound immune dysregulation in BD, particularly highlighting the immune systems role as a complex signalling network.

neuroscience↗

bioRxiv2026

Spatial engineering of posterior organizers in cerebral organoids via controlled morphogen exposure within hydrogels

Cerebral cortex organoids are powerful in vitro models that recapitulate key features of human development. However, conventional methods produce cortical organoids with spontaneous, spatially disorganized cortical regions due to limited control over morphogen distribution within local environments. Here, we present a spatially engineered hydrogel platform that drives localized posterior organizer formation in cortical organoids through controlled, localized exposure to morphogens. Using a combination of bulk photopolymerization, thermal crosslinking, and digital light processing (DLP) approaches, we fabricated hydrogels with stiffness-controlled layers that preferentially deliver morphogens to one side of the organoid, selectively inducing posterior organizer formation on the exposed face. We further validated this platform by delivering fluorescently tagged dextran, used as molecular weight-matched model morphogens, to visualize spatiotemporal delivery dynamics at the organoid interface. As a proof of principle, we also demonstrated that DLP fabrication enables the printing of dual morphogen hubs, serving as a model for establishing two opposing gradients within a single organoid. Together, this hydrogel platform enables systematic spatial patterning of cell populations in organoids, more faithfully recapitulating the spatial organization and cellular diversity of native tissues and advancing higher-fidelity models for studying human development and disease.

bioengineering↗

bioRxiv2026

Reproducible and shareable bioinformatics pipelines from natural-language prompts

Large language models (LLMs) are increasingly used to generate bioinformatics pipelines and to carry out analyses from natural-language prompts. However, the resulting analyses are often difficult to reproduce across sessions, owing to the non-deterministic nature of LLM-driven conversations and heterogeneity of local execution environments, and cannot run on remote high-performance computing (HPC) servers or be shared and reused. We present Autopipe, a platform that guides any Model Context Protocol (MCP) - compatible LLM to produce, execute, and publish source-preserved, re-executable containerized pipelines. Autopipe enables users to execute bioinformatics pipelines on any on-premises remote servers - supported by comprehensive setup documentation aimed at researchers without prior server-administration experience - and to visualize results through an extensible web-based viewer. The Autopipe platform comprises four components: a desktop application with an embedded MCP server for pipeline management and remote execution, an online registry for pipeline and plugin discovery, a web-based result viewer, and a CLI tool for customizing viewer plugins. Autopipe turns conversational analysis into re-executable and shareable workflows. Autopipe is freely available at https://autopipe.org/.

bioinformatics↗

bioRxiv2026

Partial EMT Drives Persistent Collective Migration via Collision Guidance in Heterogeneous Populations

The epithelial-mesenchymal transition (EMT) alters cell-cell interactions to facilitate collective or individual migration during embryonic development, wound repair, or tumor invasion. Epithelial cells are typically cohesive and stationary while mesenchymal cells are individually dispersed and motile. Additional "partial" EMT states are thought to occur with distinct adhesive and migratory behaviors, but these functional phenotypes are poorly understood. Here, we show that cells treated with moderate TGF-{beta} concentration exhibit collective migration that is fast and directionally persistent despite heterogeneity in epithelial, partial, and mesenchymal states. We find cells coordinate their motility by reorienting in similar directions after transient contacts, a distinct "collision guidance" mechanism that differs from epithelial arrest or mesenchymal repulsion. Moreover, partial EMT cells sustain collision guidance when interacting with epithelial or mesenchymal cells, which otherwise have increased tendency to repel. We corroborate these experimental observations with a computational model using self-propelled interacting particles that align their motion or repel upon contact. Finally, we show that partial EMT enables tissue monolayer fronts to overwhelm and displace monolayers of other cell types after collision. Overall, these results reveal that partial EMT promotes coherent and emergent behaviors that bridge from cell to tissue length scales, with potential implications for shaping epithelial tissue formation, regeneration, or disorganization.

biophysics↗

bioRxiv2026

A Rapidly Excretable, ROS-Scavenging Ionizable Lipid Decouples mRNA Delivery Potency from Toxicity

The broader clinical application of mRNA therapeutics remains constrained by dose-limiting toxicities, vector-associated immunogenicity, and prolonged tissue retention of lipid nanoparticles (LNPs) in vivo. Here, we report a class of ionizable lipids incorporating a sulfur-bearing hexyl 2-hydroxyethyl sulfide (HHES) motif that decouples mRNA delivery potency from these safety liabilities through dual functionality: the sulfur moiety acts as an intrinsic reactive oxygen species scavenger to suppress oxidative stress, while undergoing oxidative conversion into hydrophilic metabolites to promote rapid systemic clearance. HHES-based LNPs demonstrated a 3.3-fold shorter hepatic half-life and 29-fold lower total hepatic exposure than MC3, while maintaining robust protein expression including functional monoclonal antibody production in vivo. Repeated dosing in non-human primates confirmed negligible systemic, hepatic, or hematological toxicity. Leveraging this safety profile, subretinal HHES LNP delivery achieved up to 57% genome editing efficiency in retinal pigment epithelium, suppressing choroidal neovascularization by [~]65% in a wet age-related macular degeneration model without structural damage or microglial activation. This dual-function design provides a generalizable framework for safe, transient, non-accumulative mRNA nanomedicines.

bioengineering↗

bioRxiv2026

Ultrasensitive Detection of Alpha-Synuclein Oligomers in Human Plasma Using Optimized Nano-QuIC

Early diagnosis of Parkinsons disease (PD) is critical, as clinical symptoms typically emerge only after substantial neuronal loss. While -synuclein (-Syn) oligomers in blood are promising biomarkers for early detection, their clinical utility is limited by their low abundance and the presence of inhibitory components in the plasma matrix. To address these limitations, we tailored the Nanoparticle-enhanced Quaking-Induced Conversion (Nano-QuIC) platform specifically for the ultrasensitive detection of -Syn oligomers in human plasma. We identified critical reaction determinants by investigating buffer pH, ionic strength, detergent types, and shaking conditions. Furthermore, the integration of silica nanoparticles (siNPs) proved essential in mitigating plasma matrix interference, ensuring robust and reproducible protein aggregation. Under these optimized conditions, the assay achieved a detection limit of 100 pg/mL for -Syn oligomers spiked into human plasma. These results demonstrate that our adapted Nano-QuIC platform provides a highly sensitive and minimally invasive method for detecting pathological -Syn species, offering a significant advancement toward the development of early-stage PD diagnostics.

bioengineering↗

bioRxiv2026

A cross-species single-cell epigenome kidney atlas identifies epithelial cells as a driver of epigenetic aging

Epigenetic aging is a hallmark of chronic diseases, arising from sustained injuries and unresolved repairs. To investigate cell-type-specific epigenetic alterations, we built a cross-species single-cell multi-omics atlas of DNA methylomes, chromatin accessibilities, and transcriptomes on healthy, injured (human) and aging (mouse) kidneys. We identified accelerated epigenetic aging dominated by tubular epithelia in diseased kidneys. The pathological state mirrors transcriptional trajectories observed in normal aging, driven by the preferential dysregulation of lineage-specific genes lacking CpG islands. Spatially, these epigenetic changes mapped to pathological niches of failed repair. Co-profiling of single-cell DNA methylation and 3D genome architecture revealed that epithelial repair states in disease undergo significant higher-order genome reorganizations, activating genes associated with renal decline. Our findings demonstrate that epithelial aging is driven by a collapse of 3D chromatin structure and local methylome integrity, which silences cell identity and promotes a non-resolving repair state.

genomics↗

bioRxiv2026

Memory erasure by dopamine-gated retrospective learning

Erasing outdated memories is crucial for adaptive behavior. Yet once a cue-outcome association is learned, repeated cue exposure without outcome suppresses conditioned behavior without erasing the underlying memory. This allows rapid behavioral recovery when outcomes are reintroduced. Here, we confirm this limitation for standard "prospective extinction" protocols that present cues without the associated outcome, but show that true memory erasure is achieved by inverting the paradigm: presenting outcomes without associated cues, i.e., "retrospective extinction". We demonstrate that orbitofrontal cortex activity at outcome is necessary for the rapid behavioral recovery following prospective extinction, and that mesolimbic dopamine activity at outcome is necessary for retrospective extinction. These findings reconceptualize extinction mechanisms and suggest complementary strategies to mitigate relapse and erase maladaptive memories.

neuroscience↗

bioRxiv2026

NPEPPS segmental duplication drives position effect expression of TBC1D3 in the human brain

In humans, the TBC1D3 gene family is thought to play a critical role in the expansion of the frontal cortex by promoting neuronal proliferation during brain development. This gene family shows some of the greatest structural heterozygosity ([~]97%) with haplotype copy numbers ranging from 3-39 among different human haplotypes. This raises the question as to how a gene so crucial in the evolutionary expansion of the human frontal cortex can be so variable in the human population. Here, we characterize the regulatory architecture that explains this paradox. We show that 45-96% of TBC1D3 expression is attributable to a single paralog located at the most telomeric position at the edge of a cluster of TBC1D3 genes. We find that its >3-fold higher expression relative to other copies is driven by a 110 kbp segmental duplication that occurred [~]8.9 million years ago, relocating a partial duplication of the puromycin-sensitive aminopeptidase gene (NPEPPS), including its promoter, adjacent to this TBC1D3 locus. Using neurospheres and comparative transcriptomics of iPSC-derived cultures, we show that expression of NPEPPSP1-TBC1D3 increases as neurons differentiate as a result of alternative splicing and differential polyadenylation usage. While the fusion exists in other ape lineages, we show subsequent deletion of the NPEPPSP1 promoter in Gorilla and a separate, lineage-specific duplication in the Pan lineage ablated the production of this fusion product, rendering this position effect of TBC1D3 specific to humans.

genomics↗