Biology subjects

Yoon, B.

Publications and source records attributed to Yoon, B..

9 recordsLinked to original sources

bioRxiv2026

Cellular Morphology and Motility Defects are Conserved Phenotypes of Trisomy 21 Despite Heterogeneous Adhesion Mechanisms

Down syndrome is a neurodevelopmental disorder caused by the trisomy of human chromosome 21 (T21). Down syndrome is associated with a wide range of variable clinical features, including congenital heart defects and slow wound healing; however, intellectual disability is ubiquitous and results, in part, from altered neuronal connectivity. Here, we used three sets of control and T21 human fibroblasts, and one set of human induced pluripotent stem cell (hiPSC)-derived cortical neurons, to examine whether changes in cellular morphology and motility are consistent across cell types in Down syndrome and to elucidate the underlying mechanisms. We found that fibroblast morphology is dysregulated in all T21 fibroblast lines. Using a transwell migration assay, cellular migration is decreased in two of the three T21 fibroblast lines. T21 hiPSC-derived cortical neurons also exhibit morphological defects, including a decrease in the length of the longest neurite and growth cone area. Because of these significant changes in morphology and motility in T21 cells, we examined proteins in the focal adhesion complex, which links the intracellular cytoskeleton to the extracellular matrix and directly controls these processes. Multiple proteins in the adhesion complex, including paxillin, vinculin, talin, and RACK1, are dysregulated in T21 fibroblasts and hiPSC-derived neurons, but these changes have high inter-individual variability. Taken together, these findings suggest that altered cellular morphology and motility are conserved features of Down syndrome that arise through heterogeneous alterations in adhesion networks. Thus, this work significantly contributes to the recent literature highlighting the need for personalized medicine in Down syndrome.

cell biology↗

bioRxiv2026

Dissecting and steering cell dynamics using spatially-informed RNA velocity with veloAgent

RNA velocity enables inference of cell state transitions from single-cell transcriptomics by modeling transcriptional dynamics from spliced and unspliced mRNA. However, existing methods overlook spatial context and struggle to scale to large datasets, limiting insights into tissue organization and dynamic processes. We introduce veloAgent, a deep generative and agent-based framework that estimates gene- and cell-specific transcriptional kinetics while integrating spatial information through agent-based simulations of local microenvironments. By leveraging both molecular and spatial cues, veloAgent improves velocity accuracy and achieves sublinear memory scaling, enabling efficient analysis of large and multi-batch spatial datasets. A distinctive feature of veloAgent is its in silico perturbation module, which allows targeted manipulation of spatial velocity vectors to simulate regulatory interventions and predict their impact on cell fate dynamics. These capabilities position veloAgent as a scalable and versatile framework for dissecting spatially resolved cellular dynamics and guiding cell fate manipulation across diverse biological processes.

bioinformatics↗

bioRxiv2025

Could instructor talk drive CURE effectiveness? A comparative study of instructor talk in introductory lab courses

Course-based undergraduate research experiences (CUREs) are thought to enhance students motivation to continue in college, in science, and in research. Yet, how CUREs enhance student motivation is largely undefined. Theories of instructor immediacy, self-efficacy, and task values suggest that CURE instructors may talk in ways that influence students motivational beliefs. We characterized the non-content related talk of instructors teaching 48 introductory biology lab courses, half CUREs and half non-CUREs. We identified 14 types of instructor talk that fit these theoretical perspectives: fostering students closeness with their instructor (i.e., immediacy talk), building students confidence in their scientific abilities (i.e., self-efficacy talk), and promoting students sense of worth in their work (i.e., task value talk). Course type had a medium effect on talk type, with CURE instructors utilizing more immediacy, self-efficacy, and task values talk than non-CURE instructors but also showing more variation in these types of talk. Our results suggest that motivation-related instructor talk is more prevalent in CUREs than non-CUREs, but wide variation in CURE instructor talk indicates additional investigation is needed before non-content talk can be considered a mechanism for the motivational influences of CUREs. HIGHLIGHTThis study compares non-content instructor talk in CURE and non-CURE lab courses using immediacy, self-efficacy, and task value theories. CURE instructors use more talk than non-CURE instructors, but variation in CURE instructor talk leaves open the question of whether talk is a causal factor in the motivational influence of CURE instruction.

scientific communication and education↗

bioRxiv2024

The intersection of inflammation and DNA damage as a novel axis underlying the pathogenesis of autism spectrum disorders

Autism spectrum disorders (ASD) affects 1 in 36 children and is characterized by repetitive behaviors and difficulties in social interactions and social communication. The etiology of ASD is extremely heterogeneous, with a large number of ASD cases that are of unknown or complex etiology, which suggests the potential contribution of epigenetic risk factors. In particular, epidemiological and animal model studies suggest that inflammation during pregnancy could lead to an increased risk of ASD in the offspring. However, the molecular mechanisms that contribute to ASD pathogenesis in relation to maternal inflammation during pregnancy in humans are underexplored. Several pro-inflammatory cytokines have been associated with increased autistic-like behaviors in animal models of maternal immune activation, including IL-17A. Using a combination of ASD patient lymphocytes and stem cell-derived human neurons exposed to IL-17A we discovered a shared molecular signature that highlights a metabolic and translational node that could lead to altered neuronal excitability. Further, our work on human neurons brings forward the possibility that defects in the DNA damage response could be underlying the effect of IL-17A on human excitatory neurons, linking exacerbated unrepaired DNA damage to the pathogenicity of maternal inflammation in connection to ASD.

neuroscience↗

bioRxiv2024

Dynamic Regulation Of The Chromatin Environment By ASH1L Modulates Human Neuronal Structure And Function

Precise regulation of the chromatin environment through post-translational histone modification modulates transcription and controls brain development. Not surprisingly, mutations in a large number of histone-modifying enzymes underlie complex brain disorders. In particular, the histone methyltransferase ASH1L modifies histone marks linked to transcriptional activation and has been implicated in multiple neuropsychiatric disorders. However, the mechanisms underlying the pathobiology of ASH1L-asociated disease remain underexplored. We generated human isogenic stem cells with a mutation in ASH1Ls catalytic domain. We find that ASH1L dysfunction results in reduced neurite outgrowth, which correlates with alterations in the chromatin profile of activating and repressive histone marks, as well as the dysregulation of gene programs important for neuronal structure and function implicated in neuropsychiatric disease. We also identified a novel regulatory node implicating both the SP and Kruppel-like families of transcription factors and ASH1L relevant to human neuronal development. Finally, we rescue cellular defects linked to ASH1L dysfunction by leveraging two independent epigenetic mechanisms that promote transcriptional activation. In summary, we identified an ASH1L-driven epigenetic and transcriptional axis essential for human brain development and complex brain disorders that provide insights into future therapeutic strategies for ASH1L-related disorders.

neuroscience↗

bioRxiv2024

An mTOR-Tfeb-Fabp7a signaling axis can be harnessed to ameliorate bag3 cardiomyopathy in adult zebrafish

Dysregulated proteostasis in cardiomyocytes is an important pathological event in BAG3 cardiomyopathy, which can be repaired by inhibiting mechanistic target of rapamycin (mTOR) for cardioprotective effects. Here, we aimed to uncover additional pathological events and therapeutic target genes via leveraging zebrafish genetics. We first assessed transcription factor EB (tfeb), a candidate gene that encodes a direct downstream phosphorylation target of mTOR signaling. We found that cardiomyocyte-specific transgenic overexpression of tfeb (Tg[cmlc2:tfeb]) is sufficient to repair defective proteostasis, attenuate accelerated cardiac senescence, a previously unrecognized phenotype in the bag3 cardiomyopathy model, and rescue cardiac dysfunction. Next, we compared cardiac transcriptomes between the Tg(cmlc2:tfeb) transgenic fish and the mtorxu015/+ mutant, and tested 4 commonly downregulated lipodystrophy genes using an F0-based genetic assay. We found that inhibition of the fatty acid binding protein a (fabp7a) gene, but not the other 3 genes, exerts therapeutic effects on bag3 cardiomyopathy. Conversely, fabp7a expression is elevated in bag3 cardiomyopathy model and cardiomyocyte-specific overexpression of fabp7a resulted in dysregulated proteostasis, accelerated cardiac senescence, as well as cardiac dysfunction. Together, these genetic studies in zebrafish uncovered Fabp7a activation and accelerated cardiac senescence as important pathological events in bag3 cardiomyopathy. The mTOR-Tfeb-Fabp7a signaling axis can be harnessed to repair these pathological changes and exert cardioprotective effects.

genetics↗

bioRxiv2024

Building plumbing influences the microdiversity and community assembly of the drinking water microbiome.

Building plumbing microbial communities can significantly influence water quality at the point of use, particularly during periods of stagnation. Thus, a fine-scale understanding of factors governing community membership and structure, as well as environmental and ecological factors shaping building plumbing microbial communities is critical. In this study, we utilized full-length 16S ribosomal RNA (rRNA) gene sequencing to investigate the microdiversity and spatial-temporal dynamics of microbial communities in commercial and residential building plumbing systems. Bacterial operational taxonomic units (OTUs) within commercial buildings exhibited much lower microdiversity relative to the same OTUs in residential buildings. Microdiversity was associated with higher persistence and relative abundance of OTUs. Interestingly, amplicon sequencing variants within the same OTUs exhibited habitat preferences based on the building type while also demonstrating varying temporal turnover patterns. Dispersal limitation disproportionately governed community assembly in commercial buildings, whereas heterogeneous selection was the dominant ecological mechanism shaping the microbial community in residential buildings. Dispersal limitation in commercial buildings is consistent with larger building sizes and greater periods of water stagnation. Interestingly, the inability to explain the extent of heterogeneous selection-driven community assembly in residential locations using measured water chemistry may suggest a disproportionately large effect of fine-scale variation in plumbing characteristics on community assembly in residential locations.

microbiology↗

bioRxiv2022

Dysregulation of The Chromatin Environment Leads to Differential Alternative Splicing as A Mechanism Of Disease In a Human Model of Autism Spectrum Disorders

Autism spectrum disorder (ASD) affects 1 in 44 children. Chromatin regulatory proteins are overrepresented among genes that contain high risk variants in ASD. Disruption of the chromatin environment leads to widespread dysregulation of gene expression, which is traditionally thought as a mechanism of disease pathogenesis associated with ASD. Alternatively, alterations in chromatin dynamics could also lead to dysregulation of alternative splicing, which is understudied as a mechanism of ASD pathogenesis. The anticonvulsant valproic acid (VPA) is a well-known environmental risk factor for ASD that acts as a class I histone deacetylase (HDAC) inhibitor. However, the precise molecular mechanisms underlying defects in human neuronal development associated with exposure to VPA are understudied. To dissect how VPA exposure and subsequent chromatin hyperacetylation influence molecular signatures involved in ASD pathogenesis, we conducted RNA sequencing (RNA-seq) in human cortical neurons that were treated with VPA. We observed that differentially expressed genes (DEGs) were enriched for mRNA splicing, mRNA processing, histone modification, and metabolism related gene sets. Furthermore, we observed widespread increase in the number and the type of alternative splicing events. Analysis of differential transcript usage (DTU) showed that exposure to VPA induces extensive alterations in transcript isoform usage across neurodevelopmentally important genes. Finally, we find that DEGs and genes that display DTU overlap with known ASD-risk genes. Together, these findings suggest that, in addition to differential gene expression, changes in alternative splicing correlated with alterations in the chromatin environment could act as an additional mechanism of disease in ASD.

neuroscience↗

bioRxiv2020

ALX1-related Frontonasal Dysplasia Results From Defective Neural Crest Cell Development and Migration

A pedigree of subjects with frontonasal dysplasia (FND) presented with bilateral oblique facial clefts and ocular phenotypes. Genome sequencing and analysis identified a L165F missense variant in the homeodomain of the transcription factor ALX1 which was imputed to be pathogenic. Induced pluripotent stem cells (iPSC) were derived from the subjects and differentiated to neural crest cells (NCC). NCC derived from ALX1L165F/L165F iPSC were more sensitive to apoptosis, showed an elevated expression of several neural crest progenitor state markers, and exhibited impaired migration compared to wild type controls. NCC migration was also evaluated in vivo using lineage tracing in a zebrafish model, which revealed defective migration of the anterior NCC stream that contributes to the median portion of the anterior neurocranium, phenocopying the clinical presentation. Analysis of human NCC culture media revealed a change in the level of bone morphogenic proteins (BMP), with a low-level of BMP2 and a high level of BMP9. Soluble BMP2 and BMP9 antagonist treatments were able to rescue the defective migration phenotype. Taken together, these results demonstrate a mechanistic requirement of ALX1 in NCC development and migration.

cell biology↗