Biology subjects

Chao, D.

Publications and source records attributed to Chao, D..

5 recordsLinked to original sources

bioRxiv2026

Ultra-flexible PINE arrays for month-long, continuous intracellular ion flux monitoring in plants with nanomolar accuracy

High-precision in vivo monitoring of ion fluxes is essential yet challenging studying plant electrophysiology such as growth regulation, signal transduction and stress responses. Existing methods for probing ion dynamics are limited by low sensitivity, high invasiveness that interferes physiological processes, and the inability to accurately resolve ion homeostasis with required spatial and temporal resolution. Here, we introduce ultraflexible, plant implantable nanoelectrode (PINE) arrays manufactured on 1.2-m-thick polymer substrates, which enable ultrasensitive and selective measurement of ionic current for month-long via scalable nanofabrication techniques. The fabricated PINE arrays have a smaller dimension than typical plant cells as well as less stiffness, facilitating minimally invasive integration with living plant cells. This subcellular-scale plant-electronic interface allows for reliable, selective detection of K+ flux with a detection limit of [~]10- M, and thus allows continuous, stable monitoring of tomato stem cells over six weeks, capturing dynamic potassium fluctuations during all key growth stages. More importantly, the method permits long-term, real-time tracking of ion-specific dynamics without disrupting plant cellular structure or altering endogenous ion concentrations. Therefore, PINE provides unprecedented access to ion homeostasis and signaling networks, making it an excellent platform for precision agriculture and a foundational tool for future digital plant engineering.

plant biology↗

bioRxiv2024

APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology

BackgroundApolipoprotein E {varepsilon}4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimers disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance to autosomal dominant Alzheimers Disease (AD). However, it remains unclear whether and how this variant exerts its protective effects. MethodsWe introduced the R136S variant into mouse Apoe (ApoeCh) and investigated its effect on the development of AD-related pathology using the 5xFAD model of amyloidosis and the PS19 model of tauopathy. We used immunohistochemical and biochemical analysis along with single-cell spatial transcriptomics and proteomics to explore the impact of the ApoeCh variant on AD pathological development and the brains response to plaques and tau. ResultsIn 5xFAD mice, ApoeCh enhances a Disease-Associated Microglia (DAM) phenotype in microglia surrounding plaques, and reduces plaque load, dystrophic neurites, and plasma neurofilament light chain. By contrast, in PS19 mice, ApoeCh suppresses the microglial and astrocytic responses to tau-laden neurons and does not reduce tau accumulation or phosphorylation, but partially rescues tau-induced synaptic and myelin loss. We compared how microglia responses differ between the two mouse models to elucidate the distinct DAM signatures induced by ApoeCh. We identified upregulation of antigen presentation-related genes in the DAM response in a PS19 compared to a 5xFAD background, suggesting a differential response to amyloid versus tau pathology that is modulated by the presence of ApoeCh. ConclusionsThese findings highlight the ability of the ApoeCh variant to modulate microglial responses based on the type of pathology, enhancing DAM reactivity in amyloid models and dampening neuroinflammation to promote protection in tau models. This suggests that the Christchurch variants protective effects likely involve multiple mechanisms, including changes in receptor binding and microglial programming.

neuroscience↗

bioRxiv2023

Schwann cell release of p11 induces sensory neuron hyperactivity in Fabry disease.

Patients with Fabry disease suffer from chronic debilitating pain and peripheral sensory neuropathy with minimal treatment options, but the cellular drivers of this pain are unknown. Here, we propose a novel mechanism by which altered signaling between Schwann cells and sensory neurons underlies the peripheral sensory nerve dysfunction we observe in a genetic rat model of Fabry disease. Using in vivo and in vitro electrophysiological recordings, we demonstrate that Fabry rat sensory neurons exhibit pronounced hyperexcitability. Schwann cells likely contribute to this finding as application of mediators released from cultured Fabry Schwann cells induces spontaneous activity and hyperexcitability in naive sensory neurons. We examined putative algogenic mediators using proteomic analysis and found that Fabry Schwann cells release elevated levels of the protein p11 (S100-A10) which induces sensory neuron hyperexcitability. Removal of p11 from Fabry Schwann cell media causes hyperpolarization of neuronal resting membrane potential, indicating that p11 contributes to the excessive neuronal excitability caused by Fabry Schwann cells. These findings demonstrate that rats with Fabry disease exhibit sensory neuron hyperexcitability caused in part by Schwann cell release of the protein p11. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=170 HEIGHT=200 SRC="FIGDIR/small/542493v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1f672f1org.highwire.dtl.DTLVardef@f42f45org.highwire.dtl.DTLVardef@14b9806org.highwire.dtl.DTLVardef@1e9bee3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Optimization and scaling of patient-derived brain organoids uncovers deep phenotypes of disease

Cerebral organoids provide unparalleled access to human brain development in vitro. However, variability induced by current culture methodologies precludes using organoids as robust disease models. To address this, we developed an automated Organoid Culture and Assay (ORCA) system to support longitudinal unbiased phenotyping of organoids at scale across multiple patient lines. We then characterized organoid variability using novel machine learning methods and found that the contribution of donor, clone, and batch is significant and remarkably consistent over gene expression, morphology, and cell-type composition. Next, we performed multi-factorial protocol optimization, producing a directed forebrain protocol compatible with 96-well culture that exhibits low variability while preserving tissue complexity. Finally, we used ORCA to study tuberous sclerosis, a disease with known genetics but poorly representative animal models. For the first time, we report highly reproducible early morphological and molecular signatures of disease in heterozygous TSC+/- forebrain organoids, demonstrating the benefit of a scaled organoid system for phenotype discovery in human disease models.

neuroscience↗

bioRxiv2018

Mate-pair Library Construction with Controlled Polymerization Enables Comprehensive Structural Rearrangement Detection

The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick-translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter ligation reaction 3 branch ligation, we evidenced that CP-AL significantly increased DNA-circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ~50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.

genomics↗