Biology subjects

Cho, D.

Publications and source records attributed to Cho, D..

15 recordsLinked to original sources

bioRxiv2026

Collagen V Presented at the Cell-Substrate Interface Mimics Substrate Stiffening to Enhance Fibroblast Traction, Adhesion Turnover, and Persistent Migration

Collagen type V (Col-V) is a minor fibrillar collagen that regulates collagen fibril assembly, and its haploinsufficiency causes classical Ehlers-Danlos syndrome, in which wound healing is delayed. Whether Col-V also changes how fibroblasts adhere to, pull on, and migrate across a collagen-presenting surface has not been tested directly. Here, we covalently coupled Col-I or Col-V to soft (2.7 kPa) silicone substrates and quantified the mechanical response of NIH/3T3 fibroblasts. On Col-V, cells generated about 1.5-fold higher traction, spread more, and formed smaller focal adhesions that each carried more force. Adhesions on Col-V assembled and disassembled faster. Single fibroblasts on Col-V migrated more slowly but more persistently, and fibroblast monolayers closed a 500 micrometer gap faster. Raising substrate stiffness to 13 kPa reproduced this phenotype on Col-I, including higher traction, larger spread area, and smaller focal adhesions, indicating that Col-V presentation produces an adhesion state that otherwise requires a stiffer substrate. In separate reconstituted collagen hydrogels, co-assembly with 10 to 20% Col-V yielded thinner, straighter fibrils, and 20% Col-V increased the indentation modulus of the gel. These results identify the collagen type presented at the cell-material interface as a design parameter that can partly substitute for bulk stiffness in controlling fibroblast traction and migration, and they suggest Col-V as a tunable component of collagen-based biomaterials.

bioengineering↗

bioRxiv2026

A shared circuit architecture for multiscale signal recognition in crickets

Communication signals often contain behaviorally relevant structure on multiple temporal scales. Short-timescale features are commonly thought to be recognized first and then integrated into longer-timescale representations. Whether a shared circuit can instead recognize multiple timescales remains unclear. Cricket calling songs provide a tractable test because millisecond-scale pulses are grouped into chirps lasting hundreds of milliseconds. We combined female phonotaxis with a mechanistic model of the identified pulse-recognition network to ask whether this circuitry can also generate chirp selectivity. In Gryllus bimaculatus, the model, originally parameterized from pulse-scale electrophysiology and behavior, recovered the main boundaries of chirp preference without fitting to chirp behavior. Coincidence detection generated the minimum chirp-duration requirement, whereas suppressive computations in the networks input neuron shaped the upper boundaries for chirp duty cycle and period. Across 14 species, varying these suppressive computations captured major differences in chirp tuning. These findings reveal a temporally interleaved serial circuit in which long-timescale selectivity begins upstream of completed short-timescale selectivity, offering an alternative to both conventional short-first hierarchies and parallel pathways.

neuroscience↗

bioRxiv2026

Ductal myofibroblasts reactivate contractile program to stabilize alveolar architecture during lung regeneration

The alveolar sac architecture is essential for efficient gas exchange and must be precisely maintained throughout life; however, how this delicate structure is preserved during adult regeneration remains poorly understood. Using a mouse pneumonectomy model, we found that Lgr6+ Hhip+ ductal myofibroblasts, a poorly characterized mesenchymal population, are indispensable for maintaining alveolar integrity during lung regrowth. Comprehensive characterization using single-cell transcriptomics, mouse genetics, and pharmacological assays demonstrated that these ductal myofibroblasts secrete myogenic factors, most notably CCN4, to reactivate a myogenic program that converts them into contractile PA-DMFs, thereby preserving alveolar architecture. Lineage-tracing further revealed that these ductal myofibroblasts originate from embryonic MCAM- SMA+ distal progenitors via subepithelial TGF-{beta} signaling, serving as a lifelong guardian of alveolar structural integrity. Notably, cross-species analysis identified an analogous population of LGR6+ fibromyocytes in human respiratory bronchioles. Together, these findings indicate ductal myofibroblasts as a developmentally programmed cell population that reactivate a contractile program to structurally support the regeneration of adult lungs.

developmental biology↗

bioRxiv2026

Stressor-Selective Sympathetic Preganglionic Modules for Organ-Biased Control

The sympathetic nervous system coordinates organ function during stress, yet the spinal organization that converts autonomic commands into selective peripheral outputs remains poorly understood. Here, we combined spatial transcriptomics, immediate early gene mapping, anatomical tracing, and functional perturbation to define the cellular logic of spinal sympathetic preganglionic neurons (SPNs) in mice. SPN transcriptomic subtypes were spatially organized by spinal segment and sex and recruited in distinct combinations by physiological stressors, revealing stressor-selective sympathetic output modules. Focusing on cold-responsive neurotensin-expressing (Nts+) SPNs in the lower thoracic spinal cord, we found that they formed a distinct output channel to the lower sympathetic trunk and aorticorenal ganglia, promoted female-biased mobilization of white adipose tissue lipids, and were required for cold tolerance when food was unavailable. These findings establish a cell-type-resolved spinal architecture that links physiological demand to organ-biased sympathetic output and identifies the preganglionic layer as a key organizer of brain-body control.

neuroscience↗

bioRxiv2026

A single-nucleus and spatial transcriptomic atlas of the Syrian hamster preoptic area across hibernation states

Hibernation is an extreme physiological state in certain mammals that is characterized by a reversible reduction in metabolic and thermogenic demands. Although the preoptic area has been implicated in the regulation of hibernation, comprehensive molecular and spatial resources for this brain region in hibernating mammals remain limited. Here, we present an integrated transcriptomic resource of the preoptic area generated using single-nucleus RNA sequencing (snRNA-seq) and Xenium-based spatial transcriptomics in a mammalian hibernator, Syrian hamster. The resource includes cross-species transcriptomic annotations relative to mouse preoptic area datasets, seasonal snRNA-seq datasets obtained under non-hibernating and hibernating conditions, and spatially resolved cell-type annotations generated from Xenium profiling. Together, these datasets provide a reference framework for identifying neuronal populations, examining molecular conservation across species and conditions, and integrating transcriptomic identity with spatial organization.

neuroscience↗

bioRxiv2026

A reabsorption mechanism in Drosophila renal tubules maintains amino acid homeostasis

The kidney plays a central role in maintaining systemic homeostasis by regulating the excretion of metabolic compounds. In mammals, this is achieved through filtration followed by selective reabsorption, whereas insect Malpighian tubules (MTs) are thought to function primarily through active secretion. Although reabsorption of ions and water has been described in MTs, whether these tissues regulate metabolite balance through reabsorption remains unclear. Here, we uncover an amino acid (AA) reabsorption mechanism in Drosophila MTs. Quantification of AAs in excreta reveals that AA excretion changes rapidly and markedly in response to dietary protein levels, while systemic AA levels remain stable. Using ex vivo assays, we show that MTs actively transport AAs. We identify the AA transporter Slimfast (Slif), expressed in the lower tubule, as a key mediator required to maintain systemic levels of basic AAs. These findings reveal a previously unrecognised reabsorption-based strategy in insect renal tubules that functionally parallels mammalian kidney physiology, despite their distinct organisation. Our study demonstrates that AA excretion forms an additional layer to achieve metabolic homeostasis.

physiology↗

bioRxiv2026

Transcriptomic Landscape of Microglia in Mouse Models of Social Dysfunction and Oxytocin-Mediated Recovery

Atypical sociability is a hallmark of neurodevelopmental disorders arising from genetic susceptibility and prenatal environmental perturbations affecting diverse brain cell types. Using single-cell transcriptomics, we previously identified selective vulnerability of parvocellular oxytocin (OT) neurons in the paraventricular hypothalamus (PVH) following embryonic exposure to valproic acid (VPA), a teratogen that induces social deficits. Neonatal chemogenetic activation of OT neurons rescued these behavioral abnormalities and partially restored dysregulated gene expression. However, the effects of VPA exposure and OT neuron stimulation on non-neuronal PVH cells remained unclear. Here, we show that VPA induces transcriptional abnormalities in PVH microglia. Spatial transcriptomics revealed altered distributions of PVH microglial subtypes. Notably, neonatal OT neuron stimulation reversed a subset of VPA-induced microglial gene downregulation, while pharmacological manipulation of microglia normalized aberrant OT gene expression in putative parvocellular OT neurons. These findings support bidirectional OT neuron-microglia interactions that may underlie social dysfunction following embryonic VPA exposure. HighlightsO_LIEmbryonic VPA exposure induces potent transcriptional changes in PVH microglia C_LIO_LIPVH microglia comprise two spatially organized subtypes disrupted by VPA C_LIO_LINeonatal OT neuron stimulation restores gene expression in a microglial subtype C_LIO_LIMicroglial manipulation rescues OT ligand in parvocellular PVH neurons C_LI

neuroscience↗

bioRxiv2025

Reduced melanocortin tone mediates increased feeding during pregnancy in mice

During pregnancy mammals increase their food intake to accommodate the elevated metabolic demands associated with fetal growth and development. However, the molecular and neural circuit mechanisms mediating increased feeding during pregnancy are largely unknown. Here, we demonstrate that arcuate nucleus agouti-related peptide (AgRP) neurons are activated and pro-opiomelanocortin (POMC) neurons are inhibited during pregnancy in mice. These changes are required for promoting hyperphagia during pregnancy as chemogenetic inhibition of AgRP neurons or activation of POMC neurons both reduced the feeding of pregnant mice to non-pregnant levels. Finally, we utilized single cell resolution spatial transcriptomics in the arcuate nucleus of non-pregnant and pregnant mice to characterize pregnancy-induced changes in the transcriptomic state of arcuate nucleus neurons, including significant changes in both AgRP and POMC neurons. Together, these findings outline a circuit mechanism mediating increased feeding during pregnancy, providing important mechanistic insights related to conditions at the intersection of reproduction and metabolism. HighlightsO_LIAgRP neuron activity is increased and POMC neuron activity is decreased in pregnant mice C_LIO_LIIncreased AgRP neuron activity and reduced POMC neuron activity is required for increased feeding during pregnancy C_LIO_LIPregnancy enhances responsivity of AgRP neurons to palatable food C_LIO_LIPregnancy drastically alters the transcriptional state of both AgRP and POMC neurons towards positive energy balance C_LI

neuroscience↗

bioRxiv2024

Direct Intercellular Vesicle Exchange between Adjacent Cells

Intercellular communication plays a central role in the development and integrity of multicellular organisms. Vesicle transfer, especially through extracellular space, has recently been highlighted as a critical intercellular communication modality, carrying nucleic acids, proteins, and others to distant cells. Previously, we demonstrated that extracellular vesicles induce "phenotypic synchronization of cells (PSyC)" during stem cell differentiation. While examining the mechanism underlying PSyC, we discovered a novel form of cellular communication mediated by direct intercellular vesicle exchange (DIVE) between adjacent cells across the plasma membrane (PM). By achieving cell-wide and high-spatiotemporal resolution imaging of vesicles labeled with fusion proteins of CD63 or CD81 to StayGold, a photostable fluorescent marker, we observed small vesicles (50-500 nm in diameter) directly transferred between adjacent cells. These vesicles moved at approximately 1 {micro}m/s and crossed PM in approximately 10-20 seconds. Furthermore, multiple vesicles traversed nearly identical sites of PM, suggesting the presence of specific routes or structures, potentially including a pore, mediating the vesicle transfer. Three-dimensional electron microscopy provided supportive observations for traversing vesicles with single membrane. These vesicles, named InterCellular Vesicles (InterCVs), were observed to colocalize with nucleic acids, including mRNA, microRNA, and DNA, suggesting the exchange of nucleic acid-mediated information, potentially inducing PSyC, between adjacent cells. Our discovery, DIVE, reveals a previously unknown modality of cell-cell communication, with the potential to reshape our understanding of cellular biology.

cell biology↗

bioRxiv2024

Neuroanatomical dissection of the MC3R circuitry regulating energy rheostasis

Although mammals resist both acute weight loss and weight gain, the neural circuitry mediating bi-directional defense against weight change is incompletely understood. Global constitutive deletion of the melanocortin-3-receptor (MC3R) impairs the behavioral response to both anorexic and orexigenic stimuli, with MC3R knockout mice demonstrating increased weight gain following anabolic challenges and increased weight loss following anorexic challenges (i.e. impaired energy rheostasis). However, the brain regions mediating this phenotype remain incompletely understood. Here, we utilized MC3R floxed mice and viral injections of Cre-recombinase to selectively delete MC3R from medial hypothalamus (MH) in adult mice. Behavioral assays were performed on these animals to test the role of MC3R in MH in the acute response to orexigenic and anorexic challenges. Complementary chemogenetic approaches were used in MC3R-Cre mice to localize and characterize the specific medial hypothalamic brain regions mediating the role of MC3R in energy homeostasis. Finally, we performed RNAscope in situ hybridization to map changes in the mRNA expression of MC3R, POMC, and AgRP following energy rheostatic challenges. Our results demonstrate that MC3R deletion in MH increased feeding and weight gain following acute high fat diet feeding in males, and enhanced the anorexic effects of semaglutide, in a sexually dimorphic manner. Additionally, activation of DMH MC3R neurons increased energy expenditure and locomotion. Together, these results demonstrate that MC3R mediated effects on energy rheostasis result from the loss of MC3R signaling in the medial hypothalamus of adult animals and suggest an important role for DMH MC3R signaling in energy rheostasis. Key Points: O_LIMC3R signaling regulates energy rheostasis in adult mice C_LIO_LIMedial hypothalamus regulates energy rheostasis in adult mice C_LIO_LIEnergy rheostasis alters mRNA levels of AgRP and MC3R in DMH C_LIO_LIDMH MC3R neurons increase locomotion and energy expenditure C_LIO_LIMC3R expression in DMH is sexually dimorphic C_LI

neuroscience↗

bioRxiv2023

Whole-genome sequences reveal zygotic composition in chimeric twins

The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified on mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin families to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.

genomics↗

bioRxiv2023

3-phenyllactic acid promotes healthspan through SKN-1/ATFS-1-mediated mitochondrial activation and stress resilience

The mechanisms underlying the impact of probiotic supplementation on health remain largely elusive. While previous studies have primarily focused on the discovery of novel bioactive bacteria and alterations in the microbiome environment to explain potential probiotic effects, our research delves into the role of living lactic acid bacteria (LAB) and their conditioned media, highlighting that only the former, not dead bacteria, enhance the healthspan of Caenorhabditis elegans. To elucidate the underlying mechanisms, we conducted transcriptomic profiling through RNA-seq analysis in C. elegans exposed to LAB or 3-phenyllactic acid (PLA), mimicking the presence of key candidate metabolites of LAB and evaluating healthspan. Our findings reveal that PLA treatment significantly extends the healthspan of C. elegans by promoting energy metabolism and stress resilience in a SKN-1/ATFS-1-dependent manner. Moreover, PLA-mediated longevity is associated with a novel age-related parameter, the Healthy Aging Index (HAI), introduced in this study, which comprises healthspan-related factors such as motility, oxygen consumption rate (OCR), and ATP levels. Extending the relevance of our work to humans, we observed an inverse correlation between blood PLA levels and physical performance in patients with sarcopenia, when compared to age-matched non-sarcopenic controls. Our investigation thus sheds light on the pivotal role of the metabolite PLA in probiotics-mediated enhancement of organismal healthspan, and also hints at its potential involvement in age-related sarcopenia. These findings warrant further investigation to delineate PLAs role in mitigating age-related declines in healthspan and resilience to external stressors. HighlightsO_LIMetabolites Produced by Lactic Acid Bacteria Function as Mediators of Longevity in C. elegans C_LIO_LI3-Phenyllactic Acid (PLA) Augmented Lifespan Extension and Elevated the Healthy Aging Index (HAI) C_LIO_LIPLA Facilitated Healthy Aging by Inducing Mitochondrial Activation and Stress Resistance Dependent on SKN-1/ATFS-1 C_LIO_LIPatients with Sarcopenia and Symptoms of Frailty Exhibited Reduced Blood PLA Levels. C_LI

molecular biology↗

bioRxiv2023

Multifunctional Materials Strategies for Enhanced Safety of Wireless, Skin-Interfaced Bioelectronic Devices

Many recently developed classes of wireless, skin-interfaced bioelectronic devices rely on conventional thermoset silicone elastomer materials, such as poly(dimethylsiloxane) (PDMS), as soft encapsulating structures around collections of electronic components, radio frequency antennas and, commonly, rechargeable batteries. In optimized layouts and device designs, these materials provide attractive features, most prominently in their gentle, noninvasive interfaces to the skin even at regions of high curvature and large natural deformations. Past work, however, overlooks opportunities for developing variants of these materials for multimodal means to enhance the safety of the devices against failure modes that range from mechanical damage to thermal runaway. This paper presents a self-healing PDMS dynamic covalent matrix embedded with chemistries that provide thermochromism, mechanochromism, strain-adaptive stiffening, and thermal insulation, as a collection of attributes relevant to safety. Demonstrations of this materials system and associated encapsulation strategy involve a wireless, skin-interfaced device that captures mechanoacoustic signatures of health status. The concepts introduced here can apply immediately to many other related bioelectronic devices.

bioengineering↗

bioRxiv2022

L-threonine mediated DAF-16/HSF-1 activation inhibits ferroptosis and increases healthspan

The pathways that impact longevity in the wake of dietary restriction (DR) pathway remain still ill-defined. Most studies have focused on nutrient limitation and perturbations of energy metabolism to explain the beneficial effects of DR. We showed that the essential amino acid L-threonine was elevated in Caenorhabditis elegans under DR, and that L-threonine supplementation increased its healthspan. To elucidate the underlying mechanism, we conducted metabolic and transcriptomic profiling using LC-MS/MS and RNA-seq analyses in worms that were fed with RNAi to induce loss of function of key candidate mediators and evaluated healthspan. L-threonine supplementation and loss-of-threonine dehydrogenase, which govern L-threonine metabolism, increased the healthspan of C. elegans by attenuating ferroptosis in a ferritin-dependent manner. Tran-scriptomic analysis of C. elegans supplemented with L-threonine showed that FTN-1 encoding ferritin was elevated, implying FTN-1 is an essential mediator of longevity promotion through L-threonine. Organismal ferritin levels were positively correlated with chronological aging and L-thre-onine supplementation further increased ferritin levels, which protected against age-associated ferroptosis through the DAF-16 and HSF-1 pathways. Our investigation uncovered the role of a distinct and universal metabolite, L-threonine, in DR-mediated improvement in organismal healthspan, suggesting it could be an effective intervention for preventing senescence progression and age-induced ferroptosis.

cell biology↗

bioRxiv2020

Label-free bone marrow white blood cell classification using refractive index tomograms and deep learning

In this study, we report a label-free bone marrow white blood cell classification framework that captures the three-dimensional (3D) refractive index (RI) distributions of individual cells and analyzes with deep learning. Without using labeling or staining processes, 3D RI distributions of individual white blood cells were exploited for accurate profiling of their subtypes. Powered by deep learning, our method used the high-dimensional information of the WBC RI tomogram voxels and achieved high accuracy. The results show >99 % accuracy for the binary classification of myeloids and lymphoids and >96 % accuracy for the four-type classification of B, T lymphocytes, monocytes, and myelocytes. Furthermore, the feature learning of our approach was visualized via an unsupervised dimension reduction technique. We envision that this framework can be integrated into existing workflows for blood cell investigation, thereby providing cost-effective and rapid diagnosis of hematologic malignancy.

bioengineering↗